17-47290971-A-T

Position:

chr17-47290971-A-T

Variant summary

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

This summary comes from the ClinGen Evidence Repository: The c.1143A>T (p.Val381=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by phyloP score of -0.329 (BP7). The computational predictor REVEL predicts no damaging effect on ITGB3 function (BP4). The highest population minor allele frequency in gnomAD v2.1.1 is 0.006167 (123/19946 alleles) in the East Asian population, which is higher than the ClinGen PD VCEP threshold (>0.0024) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BP7, BP4 and BA1 (VCEP specifications version 2). LINK:https://erepo.genome.network/evrepo/ui/classification/CA8623176/MONDO:0100326/011

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

ITGB3
NM_000212.3 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:4

Conservation

PhyloP100: -0.320

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 -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.1143A>T	p.Val381Val	synonymous_variant	9/15	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.1143A>T	p.Val381Val	synonymous_variant	9/15	1	NM_000212.3	ENSP00000452786.2	P05106-1
ITGB3	ENST00000571680.1 linkuse as main transcript	c.1143A>T	p.Val381Val	synonymous_variant	9/9	1		ENSP00000461626.1	I3L4X8
ENSG00000259753	ENST00000560629.1 linkuse as main transcript	n.1107A>T		non_coding_transcript_exon_variant	9/18	2		ENSP00000456711.2	H3BM21
ITGB3	ENST00000696963.1 linkuse as main transcript	c.1143A>T	p.Val381Val	synonymous_variant	9/14			ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00598

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000481

AC:

121

AN:

251452

Hom.:

AF XY:

0.000456

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00625

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000116

AC:

170

AN:

1461776

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00358

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000224

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00618

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

ClinVar

Significance: Benign

Submissions summary: Benign:4

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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, reviewed by expert panel	curation	ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	Sep 07, 2023	The c.1143A>T (p.Val381=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by phyloP score of -0.329 (BP7). The computational predictor REVEL predicts no damaging effect on ITGB3 function (BP4). The highest population minor allele frequency in gnomAD v2.1.1 is 0.006167 (123/19946 alleles) in the East Asian population, which is higher than the ClinGen PD VCEP threshold (>0.0024) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BP7, BP4 and BA1 (VCEP specifications version 2). -

ITGB3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.3

DANN

Benign

0.49

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