Variant 17-4932557-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000173.7(GP1BA):c.-6-42A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,536,438 control chromosomes in the GnomAD database, including 95,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6421 hom., cov: 27)

Exomes 𝑓: 0.35 ( 88802 hom. )

Consequence

GP1BA
NM_000173.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.932

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-4932557-A-T is Benign according to our data. Variant chr17-4932557-A-T is described in ClinVar as [Benign]. Clinvar id is 1224607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GP1BA	NM_000173.7 linkuse as main transcript	c.-6-42A>T		intron_variant		ENST00000329125.6	NP_000164.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GP1BA	ENST00000329125.6 linkuse as main transcript	c.-6-42A>T		intron_variant		1	NM_000173.7	ENSP00000329380	P1
CHRNE	ENST00000649830.1 linkuse as main transcript	c.-888+1785T>A		intron_variant				ENSP00000496907

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

39042

AN:

146584

Hom.:

6419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0724

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.224

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.294

GnomAD3 exomes

AF:

0.298

AC:

66238

AN:

222086

Hom.:

11270

AF XY:

0.299

AC XY:

35779

AN XY:

119782

show subpopulations

Gnomad AFR exome

AF:

0.0612

Gnomad AMR exome

AF:

0.375

Gnomad ASJ exome

AF:

0.311

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.368

Gnomad OTH exome

AF:

0.310

GnomAD4 exome

AF:

0.351

AC:

488339

AN:

1389726

Hom.:

88802

Cov.:

AF XY:

0.347

AC XY:

238342

AN XY:

687782

show subpopulations

Gnomad4 AFR exome

AF:

0.0557

Gnomad4 AMR exome

AF:

0.369

Gnomad4 ASJ exome

AF:

0.322

Gnomad4 EAS exome

AF:

0.0941

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.314

Gnomad4 NFE exome

AF:

0.385

Gnomad4 OTH exome

AF:

0.322

GnomAD4 genome

AF:

0.266

AC:

39073

AN:

146712

Hom.:

6421

Cov.:

AF XY:

0.262

AC XY:

18678

AN XY:

71412

show subpopulations

Gnomad4 AFR

AF:

0.0722

Gnomad4 AMR

AF:

0.330

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.115

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.319

Gnomad4 NFE

AF:

0.373

Gnomad4 OTH

AF:

0.298

Alfa

AF:

0.314

Hom.:

1537

Bravo

AF:

0.261

Asia WGS

AF:

0.162

AC:

561

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.0

DANN

Benign

0.72

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