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]

Variant: NM_000173.7(GP1BA):c.1074A>G (p.Arg358=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA8314893

255463 (ClinVar)

Gene: GP1BA

Condition: Bernard-Soulier syndrome

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: edcbd259-7427-4001-8c6a-5a30e40c8e15

Approved on: 2025-02-11

Published on: 2025-02-12

HGVS expressions

NM_000173.7:c.1074A>G

NM_000173.7(GP1BA):c.1074A>G (p.Arg358=)

NC_000017.11:g.4933678A>G

CM000679.2:g.4933678A>G

NC_000017.10:g.4836973A>G

CM000679.1:g.4836973A>G

NC_000017.9:g.4777753A>G

NG_008767.2:g.6384A>G

ENST00000329125.6:c.1074A>G

ENST00000649830.1:c.-888+664T>C

ENST00000329125.5:c.1074A>G

ENST00000611961.1:c.1074A>G

NM_000173.6:c.1074A>G

Benign

BP7 BP4 BA1

BP2

Evidence Links 0

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GP1BA Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

The synonymous variant NM_000173.7(GP1BA):c.1074A>G (p.Arg358=) is not predicted by SpliceAI to impact splicing (score 0.00; BP4). In addition, it occurs at a nucleotide that is not highly conserved as shown by phyloP score of 0.134386 (BP7). The Grpmax Filtering allele frequency in gnomAD v4.1 is 0.2116 (based on 9653/44866 alleles, including 1018 homozygotes) in the East Asian population, which is higher than the ClinGen PD VCEP threshold (>0.001; BA1). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Bernard-Soulier syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP4, BP7 (ClinGen Platelet Disorders VCEP specifications version 1).

BP7

This synonymous variant is not predicted by SpliceAI to impact splicing (score 0.00). In addition, it occurs at a nucleotide that is not highly conserved as shown by phyloP score of 0.134386 (BP7).

BP4

The computational splicing predictor SpliceAI indicated that the variant has no impact on splicing (scores 0.00).

BA1

The Grpmax Filtering allele frequency in gnomAD v4.1 is 0.2116 (based on 9653/44866 alleles, including 1018 homozygotes) in the East Asian population, which is higher than the ClinGen PD VCEP threshold (>0.001), and therefore meets this criterion (BA1).

BP2

This variant has been observed in cis with the variants GP1BA c.1136_1143del and GPIBB c.124_145 del which are asserted to cause BSS in the respective patients (PMID: 19448529 and PMID: 21699652) however pathogenicity has not yet been assessed by the ClinGen PD VCEP.

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.