{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/db77be2b-6a3a-4e5c-89bd-64d4b22f558f/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1745574676", "label": "ClinGen Hemoglobinopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for HBB Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0013517", "id": "MONDO:0013517", "label": "beta-thalassemia HBB/LCRB", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "contributionDate": { "date": "2026/4/7", "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/CA125265/MONDO:0013517/170/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "comments": "The c.14G>A(p.Trp38Ter) variant in [NM_000518.5(HBB)] is a nonsense variant predicted to cause loss of function of the protein.", "contributionDate": { "date": "2026/4/7", "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": "CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "contributionDate": { "date": "2026/4/7", "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/CA125265/MONDO:0013517/170/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "contributionDate": { "date": "2026/4/7", "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": "CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "contributionDate": { "date": "2026/4/7", "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/CA125265/MONDO:0013517/170/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "comments": "This variant has been detected in 2 individuals with β-thalassemia. Of those individuals, 1 was compound heterozygous for the variant and a pathogenic variant (c.93-1G>C) and was confirmed in trans by family testing and DNA studies, and the other was homozygous for the variant. Total PM3 points are 1.5 [PMID: 23510507; 24385817].", "contributionDate": { "date": "2026/4/7", "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": "CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "contributionDate": { "date": "2026/4/7", "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/CA125265/MONDO:0013517/170/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "comments": " The minor allele frequency in gnomAD v4.1 is 0.000001239 (2/1614108 alleles), which is lower than the ClinGen Hemoglobinopathy VCEP threshold <0.0001 for PM2_Supporting, and therefore meets this criterion [PM2_P].", "contributionDate": { "date": "2026/4/7", "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": "CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/el/0/1606", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/ei/1/1607", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "contributionDate": { "date": "2026/4/7", "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/CA125265/MONDO:0013517/170/el/0/1606/1608", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "comments": "This variant has been reported in 5 unrelated probands meeting low MCV (<79 fL), low MCH (<27 pg) and increased HbA2 (>3.5%). Total score is 0.75 [PMID: 24385817, PMID:22385009, PMID:23510507; Internal lab collaborator].", "contributionDate": { "date": "2026/4/7", "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": "CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1606/1608", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/1/1607", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1606", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "contributionDate": { "date": "2026/4/7", "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/CA125265/MONDO:0013517/170/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "comments": "The variant has been reported to segregate with disease in [2] affected family members from [2] families. (For recessive haemoglobinopathies - The total number of unaffected segregations is [1]). The LOD score is [1.33].[PMID:23510507, PMID:3006832]", "contributionDate": { "date": "2026/4/7", "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": "CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "contributionDate": { "date": "2026/4/7", "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/CA125265/MONDO:0013517/170/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "comments": "The computational predictor CADD gives a PHRED score of 42, which is above threshold >12, evidence that correlates with impact to HBB function. Cannot be applied with PVS1.\n", "contributionDate": { "date": "2026/4/7", "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": "CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA125265/MONDO:0013517/170/ei/1/1778", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "contributionDate": { "date": "2026/4/7", "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/CA125265/MONDO:0013517/170/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50052_EP177555712278789", "id": "CG-PCER-AGENT:CG_50052_EP177555712278789", "type": "Agent" }, "contributionDate": { "date": "2026/4/7", "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": "CA125265/MONDO:0013517/170/ci/CA125265/MONDO:0013517/170.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170/0/1777", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA125265/MONDO:0013517/170", "metadata": { "created": "2026-04-07T13:47:31.126Z", "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, 07 Apr 2026 13:47:31 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "db77be2b-6a3a-4e5c-89bd-64d4b22f558f", "variant": { "@id": "https://reg.genome.network/allele/CA125265", "id": "CAR:CA125265", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000518.5:c.114G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000518.5(HBB):c.114G>A (p.Trp38Ter)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-28T11:32:36.649Z" } }, "status": { "code": 200, "name": "OK" } }