{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/e590fca4-0674-4996-8eaf-ad5cd2c49e4b/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1536422161", "label": "ClinGen Glaucoma Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CYP1B1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0800472", "id": "MONDO:0800472", "label": "CYP1B1-related glaucoma with or without anterior segment dysgenesis", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1649", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "3 affected segregations with a CYP1B1-related phenotype have been reported (PMID: 9497261), which fulfilled PP1_Strong. There were more family studies published than presented here.\n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1648", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1691", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "The REVEL score = 0.795, which was within the 0.773-0.931 range for PP3_Moderate, predicting a damaging effect on CYP1B1 function. \n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1690", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "The highest minor allele frequency of this variant was in the Middle Eastern genetic ancestry group of gnomAD (v4.1) = 0.006305 (33 alleles out of 5234), which did not meet the ≥ 0.01 threshold set for BS1.\n\n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1768", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1769", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1768/1770", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "Non-segregation involving this variant has not been reported.\n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1768/1770", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1769", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1768", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1654", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1655", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1654/1656", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This criterion did not apply to this variant.\n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1654/1656", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1655", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1654", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "A previous study (PMID: 18470941) demonstrated that the Gly61Glu protein had reduced 17B Estradiol Activity levels compared to wild type CYP1B1 protein and another study (PMID: 12807732) demonstrated that the protein had reduced Benzo[a]pyrene Activity levels compared to wild type CYP1B1 protein. Both studies met the OddsPath threshold for PS3_Supporting (> 2.1), indicating that this variant did impact protein function. This variant was also assessed in PMIDs: 11740343, 19793111, 19234632, 27243976, however the assays reported did not meet the OddsPath threshold (> 2.1) or the threshold for abnormal impact on protein function in the assay could not be determined.", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1669", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1670", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1669/1671", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This variant has been identified in eight individuals with a CYP1B1-related phenotype. Five individuals are compound heterozygous for the variant and a pathogenic or likely pathogenic variant (1 confirmed in trans and 4 phase unknown). Three individuals are homozygous (2 consanguineous and 1 non-consanguineous) for the variant (PMIDs: 9497261, 12372064, 16490498, 19234632, 22128238, 30270463). Total points = 4, meeting PM3_Very strong. There were more cases published than presented here.\n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1669/1671", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1670", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1669", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This missense variant is located in the hinge region, meeting PM1.\n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "No other likely pathogenic or pathogenic missense variant at this amino acid residue has been identified.", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1591", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1592", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1591/1593", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This criterion did not apply to this variant.\n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1591/1593", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1592", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1591", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "The highest minor allele frequency of this variant was in the Middle Eastern genetic ancestry group of gnomAD (v4.1) = 0.006305 (33 alleles out of 5234), which did not meet the ≤ 0.0005 threshold set for PM2_Supporting.\n\n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This criterion did not apply to this variant.\n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This criterion was not met as PP3 has been met.\n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1778", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This variant did not meet the ≥ 0.05 minor allele frequency threshold in gnomAD (v4.1).\n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1777", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1765", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1766", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1765/1767", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "An established likely pathogenic or pathogenic variant causing this same amino acid change has not been identified. ", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1765/1767", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1766", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1765", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1663", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/ei/1/1664", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA254237/MONDO:0800472/104/el/0/1663/1665", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This variant has not been identified de novo.\n", "contributionDate": { "date": "2025/11/18", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA254237/MONDO:0800472/104/ci/CA254237/MONDO:0800472/104.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1663/1665", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/1/1664", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104/0/1663", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA254237/MONDO:0800472/104", "metadata": { "created": "2025-11-18T22:04:51.779Z", "note": "DISCLAIMER: While the data/content in this document is approved by ClinGen expert panel(s), the SEPIO schema presented here is an initial prototype and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema.", "producedAtUTC": "Tue, 18 Nov 2025 22:04:51 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "e590fca4-0674-4996-8eaf-ad5cd2c49e4b", "variant": { "@id": "https://reg.genome.network/allele/CA254237", "id": "CAR:CA254237", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000104.4:c.182G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000104.4(CYP1B1):c.182G>A (p.Gly61Glu)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-04-04T04:53:17.322Z" } }, "status": { "code": 200, "name": "OK" } }