{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/0c07af21-2a6a-4805-b8d8-17f1b45fc8e3/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/CA10550392/MONDO:0018544/105/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10550392/MONDO:0018544/105/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/15", "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/CA10550392/MONDO:0018544/105/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10550392/MONDO:0018544/105/ci/CA10550392/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": "This variant does not reside within a region of ABCD1 that is defined as a\nmutational hotspot or critical functional domain by the ClinGen Peroxisomal Disorders.", "contributionDate": { "date": "2026/4/15", "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": "CA10550392/MONDO:0018544/105/ci/CA10550392/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10550392/MONDO:0018544/105/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10550392/MONDO:0018544/105/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/15", "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/CA10550392/MONDO:0018544/105/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10550392/MONDO:0018544/105/ci/CA10550392/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": "The computational predictor REVEL gives a score of 0.638, which is above the BP4 threshold of 0.5., but below the PP3 threshold of 0.85. The SpliceAI score for acceptor loss was 0.01, while donor loss, acceptor gain, and donor gain was 0.00, which is less than the ClinGen Peroxisomal Disorders threshold of ≤ 0.2 for BP4. The results from 2 in silico predictors, REVEL and SpliceAI, do not agree, providing no evidence that correlates with a damaging or benign impact on ABCD1 function.\n\n\n", "contributionDate": { "date": "2026/4/15", "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": "CA10550392/MONDO:0018544/105/ci/CA10550392/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10550392/MONDO:0018544/105/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10550392/MONDO:0018544/105/ei/1/1778", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/15", "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/CA10550392/MONDO:0018544/105/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10550392/MONDO:0018544/105/ci/CA10550392/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": "The GrpMax filtering allele frequency in gnomAD v4.1 is 0.0003710 (19/33487 alleles) in the East Asian population with 6 hemizygotes, which is higher than the ClinGen Peroxisomal Disorders threshold (≥0.017% (0.00017)) for BA1. \n\nThe filtering allele frequency (the lower threshold of the 95% CI of 27/13704 (5 hemizygotes, 1 homozygote) of the c.2043C>G variant in ABCD1 is 0.001970 for East Asian chromosomes by gnomAD v21.1, which is higher than the ClinGen Peroxisomal Disorders threshold (≥0.017% (0.00017)) for BA1, and therefore meets this criterion (BA1).\n\nVariant not present in gnomAD v31.2.", "contributionDate": { "date": "2026/4/15", "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": "CA10550392/MONDO:0018544/105/ci/CA10550392/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105/0/1777", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10550392/MONDO:0018544/105/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10550392/MONDO:0018544/105/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/15", "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/CA10550392/MONDO:0018544/105/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10550392/MONDO:0018544/105/ci/CA10550392/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": "The computational predictor REVEL gives a score of 0.638, which is above the BP4 threshold of 0.5., but below the PP3 threshold of 0.85. The SpliceAI score for acceptor loss was 0.01, while donor loss, acceptor gain, and donor gain was 0.00, which is less than the ClinGen Peroxisomal Disorders threshold of ≤ 0.2 for PP4. The results from 2 in silico predictors, REVEL and SpliceAI, do not agree, providing no evidence that correlates with a damaging or benign impact on ABCD1 function.", "contributionDate": { "date": "2026/4/15", "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": "CA10550392/MONDO:0018544/105/ci/CA10550392/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105/0/1747", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10550392/MONDO:0018544/105", "metadata": { "created": "2026-04-15T14:59:57.974Z", "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": "Wed, 15 Apr 2026 14:59:57 -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": "0c07af21-2a6a-4805-b8d8-17f1b45fc8e3", "variant": { "@id": "https://reg.genome.network/allele/CA10550392", "id": "CAR:CA10550392", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000033.4:c.2043C>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000033.4(ABCD1):c.2043C>G (p.Phe681Leu)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T02:51:19.614Z" } }, "status": { "code": 200, "name": "OK" } }