17-4932600-T-C

Position:

chr17-4932600-T-C

Variant summary

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

The NM_000173.7(GP1BA):c.-5T>C variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,610,520 control chromosomes in the GnomAD database, including 16,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2284 hom., cov: 31)

Exomes 𝑓: 0.14 ( 14413 hom. )

Consequence

GP1BA
NM_000173.7 splice_region, 5_prime_UTR

Scores

Splicing: ADA: 0.01518

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.841

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=-0.54).

BP6

Variant 17-4932600-T-C is Benign according to our data. Variant chr17-4932600-T-C is described in ClinVar as [Benign]. Clinvar id is 255460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-4932600-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.253 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.-5T>C		splice_region_variant, 5_prime_UTR_variant	2/2	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.-5T>C		splice_region_variant, 5_prime_UTR_variant	2/2	1	NM_000173.7	ENSP00000329380	P1
CHRNE	ENST00000649830.1 linkuse as main transcript	c.-888+1742A>G		intron_variant				ENSP00000496907

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25631

AN:

151526

Hom.:

2283

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.159

AC:

39356

AN:

247154

Hom.:

3375

AF XY:

0.154

AC XY:

20631

AN XY:

134098

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.265

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.180

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.136

AC:

198404

AN:

1458876

Hom.:

14413

Cov.:

AF XY:

0.135

AC XY:

98070

AN XY:

725330

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.265

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

AF:

0.169

AC:

25640

AN:

151644

Hom.:

2284

Cov.:

AF XY:

0.172

AC XY:

12719

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.264

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.186

Gnomad4 NFE

AF:

0.130

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.136

Hom.:

3036

Bravo

AF:

0.172

Asia WGS

AF:

0.180

AC:

625

AN:

3476

EpiCase

AF:

0.129

EpiControl

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	This variant is associated with the following publications: (PMID: 11751671, 17029210, 22196864, 18283530, 23315997) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.015

dbscSNV1_RF

Benign

0.27

SpliceAI score (max)

0.070

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