17-4933909-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_000173.7(GP1BA):c.1305C>T(p.Thr435Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0014 ( 28 hom. )

Failed GnomAD Quality Control

Consequence

GP1BA
NM_000173.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.466

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-4933909-C-T is Benign according to our data. Variant chr17-4933909-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-4933909-C-T is described in Lovd as [Likely_benign]. Variant chr17-4933909-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.466 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP1BA	NM_000173.7 link	c.1305C>T	p.Thr435Thr	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.1305C>T	p.Thr435Thr	synonymous_variant	Exon 2 of 2	1	NM_000173.7	ENSP00000329380.5		P07359
CHRNE	ENST00000649830.1 link	c.-888+433G>A		intron_variant	Intron 1 of 10			ENSP00000496907.1		A0A3B3IRM1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

22248

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000562

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00149

Gnomad ASJ

AF:

0.00188

Gnomad EAS

AF:

0.00180

Gnomad SAS

AF:

0.00323

Gnomad FIN

AF:

0.000623

Gnomad MID

AF:

0.0179

Gnomad NFE

AF:

0.00170

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00272

AC:

350

AN:

128696

Hom.:

AF XY:

0.00307

AC XY:

213

AN XY:

69288

show subpopulations

Gnomad AFR exome

AF:

0.000313

Gnomad AMR exome

AF:

0.00290

Gnomad ASJ exome

AF:

0.00104

Gnomad EAS exome

AF:

0.00149

Gnomad SAS exome

AF:

0.00766

Gnomad FIN exome

AF:

0.00171

Gnomad NFE exome

AF:

0.00187

Gnomad OTH exome

AF:

0.000760

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00137

AC:

749

AN:

544916

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

405

AN XY:

260258

show subpopulations

Gnomad4 AFR exome

AF:

0.000410

Gnomad4 AMR exome

AF:

0.00573

Gnomad4 ASJ exome

AF:

0.00234

Gnomad4 EAS exome

AF:

0.000848

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.00199

Gnomad4 NFE exome

AF:

0.000938

Gnomad4 OTH exome

AF:

0.00100

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00117

AC:

AN:

22274

Hom.:

Cov.:

AF XY:

0.000988

AC XY:

AN XY:

11130

show subpopulations

Gnomad4 AFR

AF:

0.000559

Gnomad4 AMR

AF:

0.00149

Gnomad4 ASJ

AF:

0.00188

Gnomad4 EAS

AF:

0.00181

Gnomad4 SAS

AF:

0.00324

Gnomad4 FIN

AF:

0.000623

Gnomad4 NFE

AF:

0.00170

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0168

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

Apr 10, 2017

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.9

DANN

Benign

0.60

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