{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/c7e908f7-83da-40fe-90fb-9bd2bf8add31/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/CA341275647/MONDO:0800406/164/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341275647/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": "2026/5/1", "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/CA341275647/MONDO:0800406/164/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341275647/MONDO:0800406/164/ci/CA341275647/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": "Variant is located in the last exon and leads to an extended C-terminal missense sequence. It is unlikely to lead to NMD. PVS1 not met.", "contributionDate": { "date": "2026/5/1", "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": "CA341275647/MONDO:0800406/164/ci/CA341275647/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341275647/MONDO:0800406/164/el/0/1591", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341275647/MONDO:0800406/164/ei/1/1592", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50140_EP176315447905952", "id": "CG-PCER-AGENT:CG_50140_EP176315447905952", "type": "Agent" }, "contributionDate": { "date": "2026/5/1", "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/CA341275647/MONDO:0800406/164/el/0/1591/1593", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341275647/MONDO:0800406/164/ci/CA341275647/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 NM_000350.3:c.6820T>A variant is predicted to cause a change in the length of the protein\n(p.Ter2274Arg) due to an in-frame stop loss variant of 1 amino acid in a non-repeat region. However, the PhyloP score is 1.011, which is less than the ABCA4 VCEP threshold of ≥7.367. Therefore, PM4 is not met.", "contributionDate": { "date": "2026/5/1", "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": "CA341275647/MONDO:0800406/164/ci/CA341275647/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/0/1591/1593", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/1/1592", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/0/1591", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341275647/MONDO:0800406/164/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341275647/MONDO:0800406/164/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50140_EP176315447905952", "id": "CG-PCER-AGENT:CG_50140_EP176315447905952", "type": "Agent" }, "contributionDate": { "date": "2026/5/1", "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/CA341275647/MONDO:0800406/164/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341275647/MONDO:0800406/164/ci/CA341275647/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" }, "contributionDate": { "date": "2026/5/1", "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": "CA341275647/MONDO:0800406/164/ci/CA341275647/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341275647/MONDO:0800406/164/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341275647/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": "2026/5/1", "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/CA341275647/MONDO:0800406/164/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341275647/MONDO:0800406/164/ci/CA341275647/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 a complex ABCA4 allele [1610G>A;6820T>A], onset under 18 years of age, macular flecks on imaging and fundus autofluorescence, decreased central visual acuity, and/or macular atrophy, which is highly specific for ABCA4-related retinopathy (PMID: 32783370). Case is not counted due to ABCA4 c.1610G>A being classified as likely pathogenic using ABCA4 VCEP rules, and the uncertainty of the impact of this variant.", "contributionDate": { "date": "2026/5/1", "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": "CA341275647/MONDO:0800406/164/ci/CA341275647/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341275647/MONDO:0800406/164/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341275647/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": "2026/5/1", "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/CA341275647/MONDO:0800406/164/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341275647/MONDO:0800406/164/ci/CA341275647/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 absent from gnomAD v4.1.0 (PM2_Supporting).", "contributionDate": { "date": "2026/5/1", "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": "CA341275647/MONDO:0800406/164/ci/CA341275647/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341275647/MONDO:0800406/164/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341275647/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": "2026/5/1", "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/CA341275647/MONDO:0800406/164/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA341275647/MONDO:0800406/164/ci/CA341275647/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 confidence interval that includes 1 and does not meet the ABCA4 VCEP threshold for PS4 (PS4 not met; PMID: 35120629). ", "contributionDate": { "date": "2026/5/1", "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": "CA341275647/MONDO:0800406/164/ci/CA341275647/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA341275647/MONDO:0800406/164", "metadata": { "created": "2026-05-01T17:35:46.144Z", "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": "Fri, 01 May 2026 17:35:46 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26333-7", "id": "LN:LA26333-7", "label": "Uncertain Significance" }, "type": "VariantPathogenicityInterpretation", "uuid": "c7e908f7-83da-40fe-90fb-9bd2bf8add31", "variant": { "@id": "https://reg.genome.network/allele/CA341275647", "id": "CAR:CA341275647", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000350.3:c.6820T>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000350.3(ABCA4):c.6820T>A (p.Ter2274Arg)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-13T14:51:10.096Z" } }, "status": { "code": 200, "name": "OK" } }