{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/fc5df0f6-7626-44cf-8f1a-67bf962858a6/doc/sepio/version/1.2.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/94412666", "label": "ClinGen Leber Congenital Amaurosis/early onset Retinal Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for AIPL1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100438", "id": "MONDO:0100438", "label": "AIPL1-related retinopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397394869/MONDO:0100438/208/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397394869/MONDO:0100438/208/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/9/29", "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/CA397394869/MONDO:0100438/208/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397394869/MONDO:0100438/208/ci/CA397394869/MONDO:0100438/208.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.692, which is above the ClinGen LCA/eoRD VCEP threshold of ≥0.644 and predicts a damaging effect on AIPL1 protein function (PP3). The splicing impact predictor SpliceAI gives a score of 0.02 for acceptor gain, which is below the ClinGen LCA/eoRD VCEP recommended threshold of ≥0.2 and does not strongly predict an impact on splicing.", "contributionDate": { "date": "2025/9/29", "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": "CA397394869/MONDO:0100438/208/ci/CA397394869/MONDO:0100438/208.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397394869/MONDO:0100438/208/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397394869/MONDO:0100438/208/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/9/29", "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/CA397394869/MONDO:0100438/208/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397394869/MONDO:0100438/208/ci/CA397394869/MONDO:0100438/208.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "At least one proband harboring this variant exhibits a phenotype including diagnosis of Leber congenital amaurosis (0.5 pts) with genotyping by next-generation sequencing panel targeting more than 150 inherited retinal disease-associated genes (2 pts), which together are not sufficiently specific for AIPL1-related retinopathy to meet PP4 (total 2.5 points, PMID: 30718709).", "contributionDate": { "date": "2025/9/29", "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": "CA397394869/MONDO:0100438/208/ci/CA397394869/MONDO:0100438/208.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397394869/MONDO:0100438/208/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397394869/MONDO:0100438/208/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/9/29", "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/CA397394869/MONDO:0100438/208/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397394869/MONDO:0100438/208/ci/CA397394869/MONDO:0100438/208.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "This variant is absent from gnomAD v4.1.0 (PM2_Supporting).", "contributionDate": { "date": "2025/9/29", "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": "CA397394869/MONDO:0100438/208/ci/CA397394869/MONDO:0100438/208.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397394869/MONDO:0100438/208/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397394869/MONDO:0100438/208/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/9/29", "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/CA397394869/MONDO:0100438/208/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397394869/MONDO:0100438/208/ci/CA397394869/MONDO:0100438/208.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "This variant has been reported in at least 1 proband with early-onset severe retinal dystrophy who was compound heterozygous with the NM_014336.4:c.(?_-1)_(276+1_277-1)del variant suspected in trans (0.25 points, PMID: 30718709), which was previously classified likely pathogenic by the ClinGen LCA/eoRD VCEP. The variant has also been reported in a second proband with early-onset severe retinal dystrophy who was heterozygous with no second AIPL1 variant identified in trans (PMID: 26626312).", "contributionDate": { "date": "2025/9/29", "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": "CA397394869/MONDO:0100438/208/ci/CA397394869/MONDO:0100438/208.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208/0/1717", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397394869/MONDO:0100438/208", "metadata": { "created": "2025-09-29T19:27:11.292Z", "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": "Mon, 29 Sep 2025 19:27:11 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.2.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26333-7", "id": "LN:LA26333-7", "label": "Uncertain Significance" }, "type": "VariantPathogenicityInterpretation", "uuid": "fc5df0f6-7626-44cf-8f1a-67bf962858a6", "variant": { "@id": "https://reg.genome.network/allele/CA397394869", "id": "CAR:CA397394869", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_014336.5:c.815G>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_014336.5(AIPL1):c.815G>C (p.Arg272Pro)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T00:01:20.138Z" } }, "status": { "code": 200, "name": "OK" } }