chr17-4933925-TCAGAGCCCGCCCCCAGCCCGACC-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 4P and 16B. PVS1_StrongBP6_Very_StrongBA1

The NM_000173.7(GP1BA):c.1322_1344delCAGAGCCCGCCCCCAGCCCGACC(p.Ser441TyrfsTer49) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 859 hom., cov: 0)

Exomes 𝑓: 0.15 ( 4834 hom. )

Failed GnomAD Quality Control

Consequence

GP1BA
NM_000173.7 frameshift

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.20

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.

BP6

Variant 17-4933925-TCAGAGCCCGCCCCCAGCCCGACC-T is Benign according to our data. Variant chr17-4933925-TCAGAGCCCGCCCCCAGCCCGACC-T is described in ClinVar as [Likely_benign]. Clinvar id is 435346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP1BA	NM_000173.7 link	c.1322_1344delCAGAGCCCGCCCCCAGCCCGACC	p.Ser441TyrfsTer49	frameshift_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.1322_1344delCAGAGCCCGCCCCCAGCCCGACC	p.Ser441TyrfsTer49	frameshift_variant	Exon 2 of 2	1	NM_000173.7	ENSP00000329380.5		P07359
CHRNE	ENST00000649830.1 link	c.-888+394_-888+416delGGTCGGGCTGGGGGCGGGCTCTG		intron_variant	Intron 1 of 10			ENSP00000496907.1		A0A3B3IRM1

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

11099

AN:

27408

Hom.:

859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.495

Gnomad AMR

AF:

0.436

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.494

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.387

GnomAD3 exomes

AF:

0.109

AC:

9489

AN:

87154

Hom.:

903

AF XY:

0.100

AC XY:

4957

AN XY:

49398

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.169

Gnomad ASJ exome

AF:

0.0223

Gnomad EAS exome

AF:

0.253

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.0376

Gnomad NFE exome

AF:

0.0930

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.146

AC:

60871

AN:

417474

Hom.:

4834

AF XY:

0.153

AC XY:

34026

AN XY:

221674

show subpopulations

Gnomad4 AFR exome

AF:

0.0908

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.0812

Gnomad4 EAS exome

AF:

0.238

Gnomad4 SAS exome

AF:

0.245

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.169

GnomAD4 genome

AF:

0.405

AC:

11102

AN:

27426

Hom.:

859

Cov.:

AF XY:

0.396

AC XY:

5271

AN XY:

13326

show subpopulations

Gnomad4 AFR

AF:

0.293

Gnomad4 AMR

AF:

0.435

Gnomad4 ASJ

AF:

0.330

Gnomad4 EAS

AF:

0.380

Gnomad4 SAS

AF:

0.495

Gnomad4 FIN

AF:

0.388

Gnomad4 NFE

AF:

0.433

Gnomad4 OTH

AF:

0.393

Alfa

AF:

0.0460

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 16, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GP1BA-related disorder

Benign:1

Jun 16, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Bernard Soulier syndrome;C1280798:Pseudo von Willebrand disease;C1847711:Nonarteritic anterior ischemic optic neuropathy, susceptibility to;C3277076:Bernard-Soulier syndrome, type A2, autosomal dominant

Benign:1

Nov 03, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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