rs5917

Positions:

chr17-47284587-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BS3BA1

This summary comes from the ClinGen Evidence Repository: The c.506G>A (p.Arg169Gln) missense variant has been reported in the literature many times as the Penb antigenic epitope. However, this polymorphism has not been reported in association with Glanzmann thrombasthenia. It is present in a Latino control population at an allele frequency of 0.01439 and functional studies in CHO cells have shown no deleterious effect on surface expression or fibrinogen binding. In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1, BS3. LINK:https://erepo.genome.network/evrepo/ui/classification/CA123232/MONDO:0010119/011

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00067 ( 8 hom. )

Consequence

ITGB3
NM_000212.3 missense

Scores

Clinical Significance

Benign reviewed by expert panel B:6

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

ITGB3 (HGNC:6156): (integrin subunit beta 3) The ITGB3 protein product is the integrin beta chain beta 3. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. A given chain may combine with multiple partners resulting in different integrins. Integrin beta 3 is found along with the alpha IIb chain in platelets. Integrins are known to participate in cell adhesion as well as cell-surface mediated signalling. [provided by RefSeq, Jul 2008]

ITGB3 links:

ENSG00000259753 (HGNC:):

ENSG00000259753 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BS3

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB3	NM_000212.3 linkuse as main transcript	c.506G>A	p.Arg169Gln	missense_variant	4/15	ENST00000559488.7	NP_000203.2	P05106-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ITGB3	ENST00000559488.7 linkuse as main transcript	c.506G>A	p.Arg169Gln	missense_variant	4/15	1	NM_000212.3	ENSP00000452786.2	P05106-1
ITGB3	ENST00000571680.1 linkuse as main transcript	c.506G>A	p.Arg169Gln	missense_variant	4/9	1		ENSP00000461626.1	I3L4X8
ENSG00000259753	ENST00000560629.1 linkuse as main transcript	n.470G>A		non_coding_transcript_exon_variant	4/18	2		ENSP00000456711.2	H3BM21
ITGB3	ENST00000696963.1 linkuse as main transcript	c.506G>A	p.Arg169Gln	missense_variant	4/14			ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

156

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00701

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00229

AC:

576

AN:

251474

Hom.:

AF XY:

0.00160

AC XY:

217

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00277

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000672

AC:

982

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000569

AC XY:

414

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00705

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000495

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00103

AC:

157

AN:

152226

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.00706

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000637

Hom.:

Bravo

AF:

0.00152

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00194

AC:

235

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Glanzmann thrombasthenia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
Benign, reviewed by expert panel	curation	ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	Aug 07, 2019	The c.506G>A (p.Arg169Gln) missense variant has been reported in the literature many times as the Penb antigenic epitope. However, this polymorphism has not been reported in association with Glanzmann thrombasthenia. It is present in a Latino control population at an allele frequency of 0.01439 and functional studies in CHO cells have shown no deleterious effect on surface expression or fibrinogen binding. In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1, BS3. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 10, 2019

- -

PEN(a)/PEN(b) ALLOANTIGEN POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Nov 01, 1992

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.53

D;.

Eigen

Benign

-0.025

Eigen_PC

Benign

0.055

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

D;D

MetaRNN

Benign

0.0098

T;T

MetaSVM

Uncertain

0.025

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.94

N;.

Sift

Benign

0.15

T;.

Sift4G

Benign

0.67

T;T

Polyphen

0.92

P;.

Vest4

0.34

MVP

0.94

MPC

0.93

ClinPred

0.020

GERP RS

4.9

Varity_R

0.18

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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