Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

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Variant: NM_000488.4(SERPINC1):c.408+4C>T

CA1251431

876601 (ClinVar)

Gene: SERPINC1

Condition: antithrombin III deficiency

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 561e873f-4335-45d7-bae2-24cb46334c95

HGVS expressions

NM_000488.4:c.408+4C>T

NM_000488.4(SERPINC1):c.408+4C>T

NC_000001.11:g.173914549G>A

CM000663.2:g.173914549G>A

NC_000001.10:g.173883687G>A

CM000663.1:g.173883687G>A

NC_000001.9:g.172150310G>A

NG_012462.1:g.7830C>T

ENST00000367698.4:c.408+4C>T

ENST00000367698.3:c.408+4C>T

ENST00000487183.1:n.113+4C>T

ENST00000494024.1:n.634+4C>T

ENST00000617423.4:c.408+4C>T

NM_000488.3:c.408+4C>T

NM_001365052.1:c.264+4C>T

NM_001365052.2:c.264+4C>T

NM_001386302.1:c.408+4C>T

NM_001386303.1:c.489+4C>T

NM_001386304.1:c.408+4C>T

NM_001386305.1:c.408+4C>T

NM_001386306.1:c.408+4C>T

Likely Benign

BS1 BP4

BP7

Evidence Links 0

Expert Panel

Thrombosis VCEP

Criteria Specification Information

Criteria Specification: ClinGen Thrombosis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SERPINC1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Thrombosis VCEP

The NM_000488.4(SERPINC1):c.408+4C>T variant is an intronic variant reported at a POPMAX FAF of 0.0003794 in the South Asian population (18/30616 alleles) meeting BS1 criteria. SpliceAI and VarSEAK predict no splicing impact for this variant; however the nucleotide may be conserved based on PhyloP and PhastCons scores (BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for AT Deficiency for SERPINC1: BS1, BP4.

BS1

The c.408+4C>T intronic variant is reported at a POPMAX FAF of 0.0003794 in the South Asian population (18/30616 alleles) and meets criteria for BS1.

BP4

SpliceAI and VarSEAK predict no splicing impact.

BP7

While no splicing impact is predicted by SpliceAI and MaxEntScan, the nucleotide may be moderately conserved, with PhyloP score of 0.53 and PhastCons score of 0.0077. BP7 criteria not met.

Approved on: 2023-07-25

Published on: 2023-09-29

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