rs5919

Positions:

chr17-47287174-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP7BP4BA1

This summary comes from the ClinGen Evidence Repository: After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.882T>C (p.Pro294=), no individuals with Glanzmann thrombasthenia were reported with the variant. Moreover, the variant has a minor allele frequency of 0.2463 (4912/19940 alleles) in gnomAD, found in the East Asian population, which is considerably higher than the expected frequency of the disease (BA1). In Silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing at a nucleotide site that is not highly conserved. In conclusion the criteria BA1, BP4, and BP7 were applied to reach a classification of benign. LINK:https://erepo.genome.network/evrepo/ui/classification/CA8623073/MONDO:0100326/011

Frequency

Genomes: 𝑓 0.11 ( 1018 hom., cov: 32)

Exomes 𝑓: 0.080 ( 6043 hom. )

Consequence

ITGB3
NM_000212.3 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:6

Conservation

PhyloP100: 1.03

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 -10 ACMG points.

BP4

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

BP7

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.882T>C	p.Pro294=	synonymous_variant	6/15	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.882T>C	p.Pro294=	synonymous_variant	6/15	1	NM_000212.3	ENSP00000452786	P1	P05106-1
ITGB3	ENST00000571680.1 linkuse as main transcript	c.882T>C	p.Pro294=	synonymous_variant	6/9	1		ENSP00000461626
ITGB3	ENST00000696963.1 linkuse as main transcript	c.882T>C	p.Pro294=	synonymous_variant	6/14			ENSP00000513002		P05106-2

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15995

AN:

152084

Hom.:

1009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.0880

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0352

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0708

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.100

AC:

25242

AN:

251236

Hom.:

1723

AF XY:

0.103

AC XY:

13938

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.0567

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.245

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.0393

Gnomad NFE exome

AF:

0.0746

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0802

AC:

117232

AN:

1461626

Hom.:

6043

Cov.:

AF XY:

0.0827

AC XY:

60153

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.0613

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.0416

Gnomad4 NFE exome

AF:

0.0664

Gnomad4 OTH exome

AF:

0.0996

GnomAD4 genome

AF:

0.105

AC:

16029

AN:

152202

Hom.:

1018

Cov.:

AF XY:

0.105

AC XY:

7815

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.0879

Gnomad4 ASJ

AF:

0.147

Gnomad4 EAS

AF:

0.241

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.0352

Gnomad4 NFE

AF:

0.0708

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.0871

Hom.:

408

Bravo

AF:

0.112

Asia WGS

AF:

0.172

AC:

599

AN:

3478

EpiCase

AF:

0.0776

EpiControl

AF:

0.0820

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Glanzmann thrombasthenia

Benign:2

Benign, reviewed by expert panel	curation	ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	Dec 01, 2022	After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.882T>C (p.Pro294=), no individuals with Glanzmann thrombasthenia were reported with the variant. Moreover, the variant has a minor allele frequency of 0.2463 (4912/19940 alleles) in gnomAD, found in the East Asian population, which is considerably higher than the expected frequency of the disease (BA1). In Silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing at a nucleotide site that is not highly conserved. In conclusion the criteria BA1, BP4, and BP7 were applied to reach a classification of benign. -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

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

-0.59

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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