{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/26888b4c-1df8-4b35-91f3-b7b87f6c1a8e/doc/sepio/version/1.0.0", "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/CA8328415/MONDO:0100438/208/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328415/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/CA8328415/MONDO:0100438/208/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8328415/MONDO:0100438/208/ci/CA8328415/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 present in gnomAD v.4.1.0 at a total allele frequency of 0.00001115, with 18 / 1,614,218 total alleles, which is lower than the ClinGen LCA/eoRD VCEP PM2_Supporting threshold of <0.0004 (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": "CA8328415/MONDO:0100438/208/ci/CA8328415/MONDO:0100438/208.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328415/MONDO:0100438/208/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328415/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/CA8328415/MONDO:0100438/208/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8328415/MONDO:0100438/208/ci/CA8328415/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 a diagnosis of Leber congenital amaurosis (0.5 pts) with light-seeking behavior (1 pt) from birth (1 pt), nystagmus (1 pt), central visual acuity limited to light perception (1 pt), and relatively normal fundus appearance at age 1 year with very mild granular RPE pigmentation (0.5 pts), which together are specific for AIPL1-related retinopathy (total 4 points, PMID: 32865313, PP4).", "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": "CA8328415/MONDO:0100438/208/ci/CA8328415/MONDO:0100438/208.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328415/MONDO:0100438/208/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328415/MONDO:0100438/208/ei/1/1652", "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/CA8328415/MONDO:0100438/208/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8328415/MONDO:0100438/208/ci/CA8328415/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 homozygous for the variant (0.5 points, VCEP member-provided data). This variant has also been reported in at least 2 probands with early-onset severe retinal dystrophy who were compound heterozygous with either the NM_014336.5(AIPL1):c.834G>A (p.Trp278Ter) variant suspected in trans (0.5 points, PMID: 32865313), which was previously classified pathogenic by the ClinGen LCA/eoRD VCEP, or the NM_014336.5(AIPL1):c.190G>A (p.Gly64Arg) variant confirmed in trans (1 point, VCEP member-provided data, Blueprint Genetics), which was previously classified likely pathogenic by the ClinGen LCA/eoRD VCEP (2 total points, PM3_Strong). A fourth proband with retinal dystrophy has been reported harboring the variant in the compound heterozygous state with the NM_014336.5(AIPL1):c.364G>A (p.Gly122Arg) variant, however, additional information will be required for inclusion in PM3 (VCEP member-provided data).", "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": "CA8328415/MONDO:0100438/208/ci/CA8328415/MONDO:0100438/208.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328415/MONDO:0100438/208/el/0/1714", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328415/MONDO:0100438/208/ei/1/1715", "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/CA8328415/MONDO:0100438/208/el/0/1714/1716", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8328415/MONDO:0100438/208/ci/CA8328415/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 predicted to cause a change in the length of the protein due to an in-frame deletion encoding 1 amino acids in a non-repeat region, with at least one of the deleted base pairs highly conserved with a PhyloP conservation score of 2.5 (PM4_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": "CA8328415/MONDO:0100438/208/ci/CA8328415/MONDO:0100438/208.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208/0/1714/1716", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208/1/1715", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208/0/1714", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8328415/MONDO:0100438/208", "metadata": { "created": "2025-09-29T18:10:55.989Z", "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 18:10:55 -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": "26888b4c-1df8-4b35-91f3-b7b87f6c1a8e", "variant": { "@id": "https://reg.genome.network/allele/CA8328415", "id": "CAR:CA8328415", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_014336.5:c.724AAG[1]" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_014336.5(AIPL1):c.724AAG[1] (p.Lys243del)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-13T21:43:14.227Z" } }, "status": { "code": 200, "name": "OK" } }