rs770991996

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_000173.7(GP1BA):c.1311_1349delAGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCC(p.Glu438_Pro450del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 20002 hom., cov: 0)

Exomes 𝑓: 0.41 ( 110933 hom. )

Failed GnomAD Quality Control

Consequence

GP1BA
NM_000173.7 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 1.08

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 -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000173.7.

BP6

Variant 17-4933876-GGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCCA-G is Benign according to our data. Variant chr17-4933876-GGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCCA-G is described in ClinVar as [Benign]. Clinvar id is 255466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-4933876-GGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCCA-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP1BA	NM_000173.7 link	c.1311_1349delAGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCC	p.Glu438_Pro450del	disruptive_inframe_deletion	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.1311_1349delAGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCC	p.Glu438_Pro450del	disruptive_inframe_deletion	Exon 2 of 2	1	NM_000173.7	ENSP00000329380.5		P07359
CHRNE	ENST00000649830.1 link	c.-888+427_-888+465delTGGGGTGGTCGGGCTGGGGGCGGGCTCTGAGGTGGGCTC		intron_variant	Intron 1 of 10			ENSP00000496907.1		A0A3B3IRM1

Frequencies

GnomAD3 genomes

AF:

0.794

AC:

51619

AN:

65030

Hom.:

20005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.800

Gnomad AMI

AF:

0.823

Gnomad AMR

AF:

0.787

Gnomad ASJ

AF:

0.770

Gnomad EAS

AF:

0.600

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.741

Gnomad MID

AF:

0.754

Gnomad NFE

AF:

0.815

Gnomad OTH

AF:

0.783

GnomAD3 exomes

AF:

0.314

AC:

38907

AN:

123944

Hom.:

12864

AF XY:

0.289

AC XY:

19746

AN XY:

68284

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.448

Gnomad ASJ exome

AF:

0.176

Gnomad EAS exome

AF:

0.421

Gnomad SAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.381

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.413

AC:

317272

AN:

767336

Hom.:

110933

AF XY:

0.427

AC XY:

168203

AN XY:

393576

show subpopulations

Gnomad4 AFR exome

AF:

0.384

Gnomad4 AMR exome

AF:

0.440

Gnomad4 ASJ exome

AF:

0.491

Gnomad4 EAS exome

AF:

0.552

Gnomad4 SAS exome

AF:

0.417

Gnomad4 FIN exome

AF:

0.638

Gnomad4 NFE exome

AF:

0.384

Gnomad4 OTH exome

AF:

0.497

GnomAD4 genome

AF:

0.794

AC:

51618

AN:

65050

Hom.:

20002

Cov.:

AF XY:

0.786

AC XY:

23304

AN XY:

29644

show subpopulations

Gnomad4 AFR

AF:

0.798

Gnomad4 AMR

AF:

0.787

Gnomad4 ASJ

AF:

0.770

Gnomad4 EAS

AF:

0.600

Gnomad4 SAS

AF:

0.632

Gnomad4 FIN

AF:

0.741

Gnomad4 NFE

AF:

0.815

Gnomad4 OTH

AF:

0.780

Alfa

AF:

0.148

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jun 19, 2017

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GP1BA-related disorder

Benign:1

Jan 28, 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). -

CIC-rearranged sarcoma

Other:1

Children's Cancer Therapy Development Institute

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

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