{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/b7d65277-f3a1-4377-aaec-d7e6e8a00809/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1570648177", "label": "ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RS1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0010725", "id": "MONDO:0010725", "label": "X-linked retinoschisis", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226778/MONDO:0010725/126/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226778/MONDO:0010725/126/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/23", "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/CA226778/MONDO:0010725/126/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA226778/MONDO:0010725/126/ci/CA226778/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "This variant is present in gnomAD v4.1.0 at a frequency of 0.000002506 among hemizygous individuals, with 1 variant allele / 399,013 total hemizygous alleles, which is between the ClinGen X-linked IRD VCEP PM2_Supporting threshold of <0.000002 and BS1 threshold of >0.00002 and fails to meet these criteria.", "contributionDate": { "date": "2025/9/23", "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": "CA226778/MONDO:0010725/126/ci/CA226778/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226778/MONDO:0010725/126/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226778/MONDO:0010725/126/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/23", "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/CA226778/MONDO:0010725/126/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA226778/MONDO:0010725/126/ci/CA226778/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "This variant is present in gnomAD v.4.1.0 at a frequency of 0.000002506 among hemizygous individuals, with 1 variant alleles / 399013 total hemizygous alleles, which is between the ClinGen X-linked IRD VCEP PM2_Supporting and BS1 threshold of 0.000002 to 0.00002and fails to meet these criteria.", "contributionDate": { "date": "2025/9/23", "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": "CA226778/MONDO:0010725/126/ci/CA226778/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226778/MONDO:0010725/126/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226778/MONDO:0010725/126/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/23", "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/CA226778/MONDO:0010725/126/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA226778/MONDO:0010725/126/ci/CA226778/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "COS7 cells exogenously expressing the variant exhibit reduced RS1 secretion into the medium relative to the wild-type control (PMID: 16361673, 29851975, PS3_Supporting).", "contributionDate": { "date": "2025/9/23", "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": "CA226778/MONDO:0010725/126/ci/CA226778/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226778/MONDO:0010725/126/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226778/MONDO:0010725/126/ei/1/1691", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/23", "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/CA226778/MONDO:0010725/126/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA226778/MONDO:0010725/126/ci/CA226778/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.917, which is within the ClinGen X-linked IRD VCEP range between 0.931 to 0.773 and predicts a damaging effect on RS1 function (PP3_Moderate). The computational splicing predictor SpliceAI gives a delta score of 0.00 for all predictive splice changes, which is below the ClinGen X-linked IRD VCEP threshold of >0.2 and does not predict that the variant disrupts RS1 splicing.", "contributionDate": { "date": "2025/9/23", "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": "CA226778/MONDO:0010725/126/ci/CA226778/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/0/1690", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226778/MONDO:0010725/126/el/0/1657", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226778/MONDO:0010725/126/ei/1/1658", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/23", "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/CA226778/MONDO:0010725/126/el/0/1657/1659", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA226778/MONDO:0010725/126/ci/CA226778/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "This variant has been reported in at least 9 apparently unrelated probands meeting the PS4 requirement of a male diagnosed with X-linked retinoschisis (PMID: 19568363, PMID: 34645606, PMID: 29851975, PMID: 34828422, PMID: 30652005, PMID: 34822951, PMID: 36377647, PMID: 39462066, PMID: 33546218, PS4_VeryStrong).", "contributionDate": { "date": "2025/9/23", "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": "CA226778/MONDO:0010725/126/ci/CA226778/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/0/1657/1659", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/1/1658", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126/0/1657", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA226778/MONDO:0010725/126", "metadata": { "created": "2025-09-23T20:34:22.952Z", "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, 23 Sep 2025 20:34:22 -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": "b7d65277-f3a1-4377-aaec-d7e6e8a00809", "variant": { "@id": "https://reg.genome.network/allele/CA226778", "id": "CAR:CA226778", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000330.4:c.544C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000330.4(RS1):c.544C>T (p.Arg182Cys)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-01T03:43:36.904Z" } }, "status": { "code": 200, "name": "OK" } }