{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/ab6237c1-841a-4f44-a1ab-2dcf9c825788/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/CA285825/MONDO:0800406/164/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA285825/MONDO:0800406/164/ei/1/1685", "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/CA285825/MONDO:0800406/164/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA285825/MONDO:0800406/164/ci/CA285825/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 CADD gives a score of 0.305 which is less than or equal to the threshold of ≤17.3, evidence that does not predict a damaging effect on ABCA4 function (BP4_Moderate). This code will not be applied since BP7 is being applied at the moderate weight instead.", "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": "CA285825/MONDO:0800406/164/ci/CA285825/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA285825/MONDO:0800406/164/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA285825/MONDO:0800406/164/ei/1/1778", "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/CA285825/MONDO:0800406/164/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA285825/MONDO:0800406/164/ci/CA285825/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 0.6547, which is greater than the ClinGen ABCA4 VCEP’s threshold for BA1 (>0.163), and therefore meets this criterion (BA1).", "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": "CA285825/MONDO:0800406/164/ci/CA285825/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/0/1777", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA285825/MONDO:0800406/164/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA285825/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/CA285825/MONDO:0800406/164/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA285825/MONDO:0800406/164/ci/CA285825/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 not significantly increased compared with the prevalence in controls. The OR is 0 and the CI is 0-0 (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": "CA285825/MONDO:0800406/164/ci/CA285825/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA285825/MONDO:0800406/164/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA285825/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/CA285825/MONDO:0800406/164/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA285825/MONDO:0800406/164/ci/CA285825/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 94 individuals with ABCA4-related retinopathy. Of those individuals, 2 were compound heterozygous for the variant and a pathogenic variant (c.6445C>T p.(R2149X); c.5882G>A p.(Gly1961Glu)) and neither of those were confirmed in trans (PM3= 1 point; PMIDs: 20801516, 28002570, 28118664). However, since this variant meets BA1, PM3 is not applicable. ", "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": "CA285825/MONDO:0800406/164/ci/CA285825/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA285825/MONDO:0800406/164/el/0/1654", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA285825/MONDO:0800406/164/ei/1/1655", "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/CA285825/MONDO:0800406/164/el/0/1654/1656", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA285825/MONDO:0800406/164/ci/CA285825/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 splicing predictor SpliceAI gives this synonymous (silent) variant a delta score of 0.03 for donor gain which is below the ClinGen ABCA4 VCEP BP7 threshold of <0.1 and does not strongly predict a splicing defect. To our knowledge, there is no known conflicting minigene or other functional data available (BP7_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": "CA285825/MONDO:0800406/164/ci/CA285825/MONDO:0800406/164.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/0/1654/1656", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/1/1655", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164/0/1654", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA285825/MONDO:0800406/164", "metadata": { "created": "2026-05-26T23:13:41.628Z", "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 23:13:41 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6675-8", "id": "LN:LA6675-8", "label": "Benign" }, "type": "VariantPathogenicityInterpretation", "uuid": "ab6237c1-841a-4f44-a1ab-2dcf9c825788", "variant": { "@id": "https://reg.genome.network/allele/CA285825", "id": "CAR:CA285825", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000350.3:c.6285T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000350.3(ABCA4):c.6285T>C (p.Asp2095=)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T03:27:33.725Z" } }, "status": { "code": 200, "name": "OK" } }