{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/a7775518-d499-407b-8f43-e50d653b4edf/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1670130991", "label": "ClinGen ABCA4 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCA4 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0800406", "id": "MONDO:0800406", "label": "ABCA4-related retinopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278268/MONDO:0800406/164/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278268/MONDO:0800406/164/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50140_EP176315447905952", "id": "CG-PCER-AGENT:CG_50140_EP176315447905952", "type": "Agent" }, "contributionDate": { "date": "2026/5/26", "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/CA341278268/MONDO:0800406/164/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341278268/MONDO:0800406/164/ci/CA341278268/MONDO:0800406/164.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50140_EP176315447905952", "id": "CG-PCER-AGENT:CG_50140_EP176315447905952", "type": "Agent" }, "comments": "This is a nonsense variant located in exon 45 out of 50, and introduces a premature stop codon between codons 1-2255 (PVS1).\n", "contributionDate": { "date": "2026/5/26", "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": "CA341278268/MONDO:0800406/164/ci/CA341278268/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278268/MONDO:0800406/164/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278268/MONDO:0800406/164/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50140_EP176315447905952", "id": "CG-PCER-AGENT:CG_50140_EP176315447905952", "type": "Agent" }, "contributionDate": { "date": "2026/5/26", "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/CA341278268/MONDO:0800406/164/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341278268/MONDO:0800406/164/ci/CA341278268/MONDO:0800406/164.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50140_EP176315447905952", "id": "CG-PCER-AGENT:CG_50140_EP176315447905952", "type": "Agent" }, "comments": "This variant has been detected in at least 1 individual with ABCA4-related retinopathy. This individual was compound heterozygous for the variant and another pathogenic variant and was confirmed in trans (participant 90 has c.6319C>T and c.6213C>G; PM3 +1; PMID: 26377081). \n", "contributionDate": { "date": "2026/5/26", "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": "CA341278268/MONDO:0800406/164/ci/CA341278268/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278268/MONDO:0800406/164/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278268/MONDO:0800406/164/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50140_EP176315447905952", "id": "CG-PCER-AGENT:CG_50140_EP176315447905952", "type": "Agent" }, "contributionDate": { "date": "2026/5/26", "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/CA341278268/MONDO:0800406/164/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341278268/MONDO:0800406/164/ci/CA341278268/MONDO:0800406/164.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50140_EP176315447905952", "id": "CG-PCER-AGENT:CG_50140_EP176315447905952", "type": "Agent" }, "comments": "The total minor allele frequency in gnomAD v4.1.0 is 0.0000006195 (1/1614190 alleles), which is lower than the ClinGen ABCA4 VCEP’s threshold for PM2_Supporting (<0.0001).", "contributionDate": { "date": "2026/5/26", "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": "CA341278268/MONDO:0800406/164/ci/CA341278268/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278268/MONDO:0800406/164/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278268/MONDO:0800406/164/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50140_EP176315447905952", "id": "CG-PCER-AGENT:CG_50140_EP176315447905952", "type": "Agent" }, "contributionDate": { "date": "2026/5/26", "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/CA341278268/MONDO:0800406/164/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341278268/MONDO:0800406/164/ci/CA341278268/MONDO:0800406/164.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50140_EP176315447905952", "id": "CG-PCER-AGENT:CG_50140_EP176315447905952", "type": "Agent" }, "comments": "The prevalence of the variant in affected individuals is increased compared with the prevalence in controls. The OR is infinity, but the CI is [0.31, infinity], which does contain 1, so PS4 is not met (PMID: 35120629).", "contributionDate": { "date": "2026/5/26", "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": "CA341278268/MONDO:0800406/164/ci/CA341278268/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341278268/MONDO:0800406/164", "metadata": { "created": "2026-05-26T17:46:23.875Z", "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, 26 May 2026 17:46:23 -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": "a7775518-d499-407b-8f43-e50d653b4edf", "variant": { "@id": "https://reg.genome.network/allele/CA341278268", "id": "CAR:CA341278268", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000350.3:c.6213C>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000350.3(ABCA4):c.6213C>G (p.Tyr2071Ter)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-04T07:59:01.705Z" } }, "status": { "code": 200, "name": "OK" } }