NM_000173.7:c.1311A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP7BP4BA1

This summary comes from the ClinGen Evidence Repository: The NM_000173.7(GP1BA):c.1311A>G (p.Pro437=) synonymous variant occurs at a Grpmax filtering allele frequency of 0.8560 (based 186885/217504 alleles in the European non-Finnish population) in gnomADv4.1, which is higher than the ClinGen PD VCEP threshold (>0.001) for BA1. In silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing (delta score 0.00) and a PhyloP score of 0.011 shows that the nucleotide position is not highly conserved (BP4, BP7). 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. LINK:https://erepo.genome.network/evrepo/ui/classification/CA8314972/MONDO:0009276/079

Frequency

Genomes: 𝑓 0.62 ( 2756 hom., cov: 0)

Exomes 𝑓: 0.83 ( 99379 hom. )

Failed GnomAD Quality Control

Consequence

GP1BA
NM_000173.7 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:5

Conservation

PhyloP100: -0.124

Variant links:

Genes affected

GP1BA (HGNC:4439): (glycoprotein Ib platelet subunit alpha) Glycoprotein Ib (GP Ib) is a platelet surface membrane glycoprotein composed of a heterodimer, an alpha chain and a beta chain, that is linked by disulfide bonds. The Gp Ib functions as a receptor for von Willebrand factor (VWF). The complete receptor complex includes noncovalent association of the alpha and beta subunits with platelet glycoprotein IX and platelet glycoprotein V. The binding of the GP Ib-IX-V complex to VWF facilitates initial platelet adhesion to vascular subendothelium after vascular injury, and also initiates signaling events within the platelet that lead to enhanced platelet activation, thrombosis, and hemostasis. This gene encodes the alpha subunit. Mutations in this gene result in Bernard-Soulier syndromes and platelet-type von Willebrand disease. The coding region of this gene is known to contain a polymophic variable number tandem repeat (VNTR) domain that is associated with susceptibility to nonarteritic anterior ischemic optic neuropathy. [provided by RefSeq, Oct 2013]

GP1BA links:

CHRNE (HGNC:1966): (cholinergic receptor nicotinic epsilon subunit) Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]

CHRNE links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

For more information check the summary or visit ClinGen Evidence Repository.

BP7

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP1BA	NM_000173.7 link	c.1311A>G	p.Pro437Pro	synonymous_variant	Exon 2 of 2	ENST00000329125.6	NP_000164.5	P07359L7UYB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP1BA	ENST00000329125.6 link	c.1311A>G	p.Pro437Pro	synonymous_variant	Exon 2 of 2	1	NM_000173.7	ENSP00000329380.5		P07359
CHRNE	ENST00000649830.1 link	c.-888+427T>C		intron_variant	Intron 1 of 10			ENSP00000496907.1		A0A3B3IRM1

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

7187

AN:

11514

Hom.:

2746

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.636

Gnomad AMR

AF:

0.605

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.325

Gnomad MID

AF:

0.688

Gnomad NFE

AF:

0.591

Gnomad OTH

AF:

0.580

GnomAD3 exomes

AF:

0.369

AC:

37152

AN:

100604

Hom.:

13330

AF XY:

0.389

AC XY:

20825

AN XY:

53530

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.367

Gnomad ASJ exome

AF:

0.561

Gnomad EAS exome

AF:

0.0860

Gnomad SAS exome

AF:

0.414

Gnomad FIN exome

AF:

0.467

Gnomad NFE exome

AF:

0.388

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.828

AC:

242500

AN:

292884

Hom.:

99379

Cov.:

AF XY:

0.824

AC XY:

120707

AN XY:

146426

show subpopulations

Gnomad4 AFR exome

AF:

0.744

Gnomad4 AMR exome

AF:

0.784

Gnomad4 ASJ exome

AF:

0.761

Gnomad4 EAS exome

AF:

0.455

Gnomad4 SAS exome

AF:

0.752

Gnomad4 FIN exome

AF:

0.670

Gnomad4 NFE exome

AF:

0.864

Gnomad4 OTH exome

AF:

0.757

GnomAD4 genome

AF:

0.625

AC:

7211

AN:

11544

Hom.:

2756

Cov.:

AF XY:

0.611

AC XY:

3355

AN XY:

5494

show subpopulations

Gnomad4 AFR

AF:

0.777

Gnomad4 AMR

AF:

0.606

Gnomad4 ASJ

AF:

0.614

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.326

Gnomad4 FIN

AF:

0.325

Gnomad4 NFE

AF:

0.591

Gnomad4 OTH

AF:

0.575

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:2

Oct 25, 2016

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

May 14, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Bernard Soulier syndrome

Benign:1

Feb 11, 2025

ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: curation

The NM_000173.7(GP1BA):c.1311A>G (p.Pro437=) synonymous variant occurs at a Grpmax filtering allele frequency of 0.8560 (based 186885/217504 alleles in the European non-Finnish population) in gnomADv4.1, which is higher than the ClinGen PD VCEP threshold (>0.001) for BA1. In silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing (delta score 0.00) and a PhyloP score of 0.011 shows that the nucleotide position is not highly conserved (BP4, BP7). 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.1

DANN

Benign

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over