Variant: NM_000407.5:c.470T>C

CA410677579

Gene: GP1BB

Condition: Bernard-Soulier syndrome

Inheritance Mode: Autosomal recessive inheritance

UUID: 7f7f5632-ea89-406d-b0ad-14d5a7252cd8

Approved on: 2025-06-19

Published on: 2025-06-19

HGVS expressions

NM_000407.5:c.470T>C
NC_000022.11:g.19724313T>C
CM000684.2:g.19724313T>C
NC_000022.10:g.19711836T>C
CM000684.1:g.19711836T>C
NC_000022.9:g.18091836T>C
NG_007974.1:g.5771T>C
ENST00000366425.4:c.470T>C
ENST00000366425.3:c.470T>C
ENST00000431044.5:c.*1555T>C
NM_000407.4:c.470T>C
NR_037611.1:n.4210T>C
NR_037612.1:n.2714T>C

Uncertain Significance

• Met criteria codes: PP3 PM2_Supporting

• Not Met criteria codes: PP4

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GP1BB Version 1.0.0

Evidence submitted by expert panel

Platelet Disorders VCEP

“The c.470T>C (p.Leu157Pro) variant in GP1BB is a missense variant predicted to cause substitution of Leucine by Proline at amino acid 157 (p.Leu157Pro). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). The computational predictor REVEL gives a score of 0.680, which is above the ClinGen PD VCEP threshold of >0.644 and predicts a damaging effect on GP1BB function (PP3). At least one BSS patient (BS-9 from PMID: 21699652) is reported in the literature. This patient was not scored because they are reported to be homozygous for the c.462G>C (p.Gln154His) variant in GP1BB, homozygous c.470T>C (p.Leu157Pro) in GP1BB and heterozygous for c.1522T>C (p.Tyr508His) in GP1BA.

Met criteria codes

• PP3: The computational predictor REVEL gives a score of 0.680, which is above the ClinGen PD VCEP threshold of >0.644 and predicts a damaging effect on GP1BB function (PP3).
• PM2_Supporting: This variant is absent from gnomAD v4.1.0 (PM2_Supporting).

Not Met criteria codes

• PP4: At least one BSS patient (BS-9 from PMID: 21699652) is reported in the literature. This patient was not scored because they are reported to be homozygous for the c.462G>C (p.Gln154His) variant in GP1BB, homozygous c.470T>C (p.Leu157Pro) in GP1BB and heterozygous for c.1522T>C (p.Tyr508His) in GP1BA.