{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/d281773d-d5d8-4724-a03c-3fcfdd3448a2/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1537428517", "label": "ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0018544", "id": "MONDO:0018544", "label": "adrenoleukodystrophy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415118457/MONDO:0018544/105/el/0/1612", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415118457/MONDO:0018544/105/ei/1/1613", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/16", "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/CA415118457/MONDO:0018544/105/el/0/1612/1614", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415118457/MONDO:0018544/105/ci/CA415118457/MONDO:0018544/105.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "comments": "p.Trp679Ter creates a stop codon downstream of the last exon-junction as it is after nucleotide c.1942, leading to a loss of the last 67 aa of the total protein length which is 746 aa. 67/746 represents about 9% loss of the total protein. The transcript with this variant is not predicted to undergo NMD. Since this variant removes less than 10% of protein, a moderate strength is applied according to the PVS1 guidelines from Abou Tayoun et al., 2018 (PMID:30192042). Based on this criterion, PM4 will not be applied. Based on the ALD database the last (likely)pathogenic variant is located at position \tc.2078.", "contributionDate": { "date": "2026/4/16", "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": "CA415118457/MONDO:0018544/105/ci/CA415118457/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105/0/1612/1614", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105/1/1613", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105/0/1612", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415118457/MONDO:0018544/105/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415118457/MONDO:0018544/105/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/16", "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/CA415118457/MONDO:0018544/105/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415118457/MONDO:0018544/105/ci/CA415118457/MONDO:0018544/105.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "comments": "1 male case from a newborn screening (Matteson J et al 2021, PMID: 33920672) was positive for biochemical (C26 two tier measurement) and adrenal involvement and had long-term follow up resolution (see supplementary table), thus meeting supporting strength (A+E+F from specification table).\n", "contributionDate": { "date": "2026/4/16", "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": "CA415118457/MONDO:0018544/105/ci/CA415118457/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415118457/MONDO:0018544/105/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415118457/MONDO:0018544/105/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/16", "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/CA415118457/MONDO:0018544/105/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415118457/MONDO:0018544/105/ci/CA415118457/MONDO:0018544/105.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "comments": "p.Trp679Ter is absent in gnomAD v2.1 and v3.1. ", "contributionDate": { "date": "2026/4/16", "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": "CA415118457/MONDO:0018544/105/ci/CA415118457/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415118457/MONDO:0018544/105/el/0/1699", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415118457/MONDO:0018544/105/ei/1/1700", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/16", "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/CA415118457/MONDO:0018544/105/el/0/1699/1701", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415118457/MONDO:0018544/105/ci/CA415118457/MONDO:0018544/105.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "comments": "From PP4 description: 2 het females with age of symptoms 39/59 (Habekost CT et al., 2018, PMID: 24410807). In this study, 87% of het women were symptomatic, with neurological impairments as measured by JOA and SSPROM scores (B + E + F is considered for these het pts).", "contributionDate": { "date": "2026/4/16", "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": "CA415118457/MONDO:0018544/105/ci/CA415118457/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105/0/1699/1701", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105/1/1700", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105/0/1699", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415118457/MONDO:0018544/105", "metadata": { "created": "2026-04-16T19:17:57.135Z", "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, 16 Apr 2026 19:17:56 -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": "d281773d-d5d8-4724-a03c-3fcfdd3448a2", "variant": { "@id": "https://reg.genome.network/allele/CA415118457", "id": "CAR:CA415118457", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000033.4:c.2037G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000033.4(ABCD1):c.2037G>A (p.Trp679Ter)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-13T21:42:51.967Z" } }, "status": { "code": 200, "name": "OK" } }