{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/c19472a2-3c5b-40bc-aced-cb58564a4b6d/doc/sepio/version/2.0.0", "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/CA119128/MONDO:0800406/164/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA119128/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": "2026/1/29", "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/CA119128/MONDO:0800406/164/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA119128/MONDO:0800406/164/ci/CA119128/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 significantly increased compared with the prevalence in controls. The OR is 5.8 and the CI is 5.14-6.64, which is above the ABCA4 VCEP threshold of ≥5, where the CI does not contain 1. However, upon contacting the authors, we were informed that this calculation included individuals with the complex allele. Therefore, this value is not a true representation of the effect of this variant alone (PS4; PMID: 35120629). ", "contributionDate": { "date": "2026/1/29", "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": "CA119128/MONDO:0800406/164/ci/CA119128/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA119128/MONDO:0800406/164/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA119128/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": "2026/1/29", "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/CA119128/MONDO:0800406/164/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA119128/MONDO:0800406/164/ci/CA119128/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 0.798 which is above the threshold of >0.772, evidence that predicts a damaging effect on ABCA4 function (PP3_Moderate).", "contributionDate": { "date": "2026/1/29", "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": "CA119128/MONDO:0800406/164/ci/CA119128/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/0/1690", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA119128/MONDO:0800406/164/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA119128/MONDO:0800406/164/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50140_EP176315447905952", "id": "CG-PCER-AGENT:CG_50140_EP176315447905952", "type": "Agent" }, "contributionDate": { "date": "2026/1/29", "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/CA119128/MONDO:0800406/164/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA119128/MONDO:0800406/164/ci/CA119128/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 GroupMax filtering allele frequency in gnomAD v4.1.0 is 0.008753, which is greater than the ClinGen ABCA4 VCEP’s threshold for BS1_Supporting (>0.00163); however, this variant is on the ABCA4 BS1 Exclusion List.\n\nhttps://gnomad.broadinstitute.org/variant-cooccurrence?dataset=gnomad_r2_1&variant=1-94476467-T-A&variant=1-94517254-C-G\nCalculated frequency using haplotypes: 0.0043605693", "contributionDate": { "date": "2026/1/29", "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": "CA119128/MONDO:0800406/164/ci/CA119128/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA119128/MONDO:0800406/164/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA119128/MONDO:0800406/164/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50140_EP176315447905952", "id": "CG-PCER-AGENT:CG_50140_EP176315447905952", "type": "Agent" }, "contributionDate": { "date": "2026/1/29", "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/CA119128/MONDO:0800406/164/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA119128/MONDO:0800406/164/ci/CA119128/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": "ABCA4 ATPase activity in HEK293 cells showed an approximately 75% reduction of basal and retinal-stimulated ATPase, indicating that this variant impacts protein function (PS3_Supporting; PMID: 11017087).", "contributionDate": { "date": "2026/1/29", "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": "CA119128/MONDO:0800406/164/ci/CA119128/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA119128/MONDO:0800406/164/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA119128/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": "2026/1/29", "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/CA119128/MONDO:0800406/164/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA119128/MONDO:0800406/164/ci/CA119128/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 3 individuals with ABCA4-related retinopathy that do not report the complex allele with the ABCA4 p.Asn1868Ile variant. However, given the p.Asn1868Ile variant was at one time thought to be benign, we fear this variant is possibly under reported. Therefore, we will not count any probands until we have evidence that the p.Asn1868Ile variant was not in cis with the p. Gly863Ala variant. ", "contributionDate": { "date": "2026/1/29", "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": "CA119128/MONDO:0800406/164/ci/CA119128/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164/0/1717", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA119128/MONDO:0800406/164", "metadata": { "created": "2026-01-29T13:17:27.781Z", "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": "Thu, 29 Jan 2026 13:17:27 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26333-7", "id": "LN:LA26333-7", "label": "Uncertain Significance" }, "type": "VariantPathogenicityInterpretation", "uuid": "c19472a2-3c5b-40bc-aced-cb58564a4b6d", "variant": { "@id": "https://reg.genome.network/allele/CA119128", "id": "CAR:CA119128", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000350.3:c.2588G>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000350.3(ABCA4):c.2588G>C (p.Gly863Ala)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-04-08T15:50:38.258Z" } }, "status": { "code": 200, "name": "OK" } }