{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/e2fee552-1b60-4d0a-891c-9c095a087c26/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/CA341278913/MONDO:0800406/164/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278913/MONDO:0800406/164/ei/1/1691", "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/CA341278913/MONDO:0800406/164/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341278913/MONDO:0800406/164/ci/CA341278913/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 computational predictor REVEL gives a score of 0.935 which is above the threshold of >0.772, evidence that predicts a damaging effect on ABCA4 function (PP3_Moderate).", "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": "CA341278913/MONDO:0800406/164/ci/CA341278913/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/0/1690", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278913/MONDO:0800406/164/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278913/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/CA341278913/MONDO:0800406/164/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341278913/MONDO:0800406/164/ci/CA341278913/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 is not found in Cornelis et al. (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": "CA341278913/MONDO:0800406/164/ci/CA341278913/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278913/MONDO:0800406/164/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278913/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/CA341278913/MONDO:0800406/164/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341278913/MONDO:0800406/164/ci/CA341278913/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": "Clinvar Accession: SCV002182102.4. Adult female with ABCA4, c.6721C>G (p.Leu2241Val), c.6121G>A (p.Gly2041Ser) phase undetermined and a clinical diagnosis of Stargardt disease. Variant in trans with likely pathogenic variant, phase unconfirmed, giving only 0.25 points in PM3 for this proband which is less than the criteria to meet PM3 using ABCA4 VCEP specifications for this criterion.", "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": "CA341278913/MONDO:0800406/164/ci/CA341278913/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278913/MONDO:0800406/164/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278913/MONDO:0800406/164/ei/1/1781", "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/CA341278913/MONDO:0800406/164/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341278913/MONDO:0800406/164/ci/CA341278913/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": "Another missense variant, c.6122G>A (p.Gly2041Asp) (PMID: 2735394, 33546218, 38540785; ClinVar Variation ID 1048145), in the same codon has been classified as pathogenic for ABCA4-related retinopathy by the ClinGen ABCA4 VCEP, and Splice AI (score of 0) revealed no expected effects on splicing (PM5).", "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": "CA341278913/MONDO:0800406/164/ci/CA341278913/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278913/MONDO:0800406/164/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278913/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/CA341278913/MONDO:0800406/164/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341278913/MONDO:0800406/164/ci/CA341278913/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 (1/1614140 alleles), which is lower than the ClinGen ABCA4 VCEP’s threshold for PM2_Supporting (<0.0001), meeting this criterion (PM2_Supporting).", "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": "CA341278913/MONDO:0800406/164/ci/CA341278913/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278913/MONDO:0800406/164/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341278913/MONDO:0800406/164/ei/1/1634", "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/CA341278913/MONDO:0800406/164/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341278913/MONDO:0800406/164/ci/CA341278913/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": "At least one patient with this variant displayed presence of at least two ABCA4 variants, onset under 18 years of age, macular flecks on imaging, macular atrophy, and decreased vision acuity, which is highly specific for ABCA4-related retinopathy (PP4_Supporting, ClinVar SCV002182102.4, Invitae).", "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": "CA341278913/MONDO:0800406/164/ci/CA341278913/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164/0/1633", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341278913/MONDO:0800406/164", "metadata": { "created": "2026-05-26T17:40:28.028Z", "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 17:40:27 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "e2fee552-1b60-4d0a-891c-9c095a087c26", "variant": { "@id": "https://reg.genome.network/allele/CA341278913", "id": "CAR:CA341278913", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000350.3:c.6121G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000350.3(ABCA4):c.6121G>A (p.Gly2041Ser)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-04T09:45:57.900Z" } }, "status": { "code": 200, "name": "OK" } }