rs13306487

Positions:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BA1BP4

This summary comes from the ClinGen Evidence Repository: The NM_000212.3(ITGB3):c.1544G>A (p.Arg515Gln) missense variant occurs at an allele frequency of 0.02211 in the gnomAD East Asian population and is predicted, by REVEL score of 0.183, to have no impact on the gene or gene product. This variant has been reported in the literature multiple times (including PMIDs: 7694683 and 8457479) as the alloantigenic site HPA-6 (formerly known as Ca/Tu). In summary, the variant is classified as benign for GT. GT-specific criteria applied: BA1 and BP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA123241/MONDO:0010119/011

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 8 hom. )

Consequence

ITGB3
NM_000212.3 missense

Scores

Clinical Significance

Benign reviewed by expert panel U:1B:4

Conservation

PhyloP100: -0.931

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

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.1544G>A	p.Arg515Gln	missense_variant	10/15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7 linkuse as main transcript	c.1544G>A	p.Arg515Gln	missense_variant	10/15	1	NM_000212.3	ENSP00000452786	P1	P05106-1
ITGB3	ENST00000696963.1 linkuse as main transcript	c.1544G>A	p.Arg515Gln	missense_variant	10/14			ENSP00000513002		P05106-2

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

242

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0198

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00894

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00270

AC:

675

AN:

250376

Hom.:

AF XY:

0.00254

AC XY:

344

AN XY:

135302

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.000301

Gnomad EAS exome

AF:

0.0219

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00981

Gnomad NFE exome

AF:

0.000389

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00109

AC:

1597

AN:

1459212

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

760

AN XY:

725372

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.000307

Gnomad4 EAS exome

AF:

0.0194

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.00938

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.00241

GnomAD4 genome

AF:

0.00158

AC:

241

AN:

152352

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0197

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00894

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.00125

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00232

AC:

282

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:4

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Glanzmann thrombasthenia

Uncertain:1Benign:1

Uncertain significance, 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Benign, reviewed by expert panel	curation	ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	May 07, 2021	The NM_000212.3(ITGB3):c.1544G>A (p.Arg515Gln) missense variant occurs at an allele frequency of 0.02211 in the gnomAD East Asian population and is predicted, by REVEL score of 0.183, to have no impact on the gene or gene product. This variant has been reported in the literature multiple times (including PMIDs: 7694683 and 8457479) as the alloantigenic site HPA-6 (formerly known as Ca/Tu). In summary, the variant is classified as benign for GT. GT-specific criteria applied: BA1 and BP4. -

not provided

Benign:2

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

Ca/Tu ALLOANTIGEN POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Dec 01, 1993

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.28

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.10

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

0.45

Sift

Benign

0.47

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.086

MVP

0.81

MPC

0.47

ClinPred

0.016

GERP RS

-0.14

Varity_R

0.057

gMVP

0.39

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