17-47290971-A-C

Position:

chr17-47290971-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The ITGB3 synonymous variant NM_000212.2:c.1143A>C is very common in control population databases, with an overall allele frequency of 0.38777 in gnomAD v2.1.1. Note that initial reports of variation at this nucleotide position referred to the current reference allele as the variant at this position (c.1143C>A; PMID:8878424, PMID:20020534, and PMID:25728920), however this reported "variant" is now considered the reference allele. In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1. LINK:https://erepo.genome.network/evrepo/ui/classification/CA8623175/MONDO:0010119/011

Frequency

Genomes: 𝑓 0.39 ( 12141 hom., cov: 31)

Exomes 𝑓: 0.37 ( 102526 hom. )

Consequence

ITGB3
NM_000212.3 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:8

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 -8 ACMG points.

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

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59904

AN:

151892

Hom.:

12119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.429

Gnomad EAS

AF:

0.567

Gnomad SAS

AF:

0.462

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.420

GnomAD3 exomes

AF:

0.387

AC:

97372

AN:

251452

Hom.:

19689

AF XY:

0.392

AC XY:

53217

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.288

Gnomad ASJ exome

AF:

0.432

Gnomad EAS exome

AF:

0.584

Gnomad SAS exome

AF:

0.450

Gnomad FIN exome

AF:

0.331

Gnomad NFE exome

AF:

0.369

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.370

AC:

541056

AN:

1461434

Hom.:

102526

Cov.:

AF XY:

0.373

AC XY:

271008

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.440

Gnomad4 AMR exome

AF:

0.297

Gnomad4 ASJ exome

AF:

0.427

Gnomad4 EAS exome

AF:

0.559

Gnomad4 SAS exome

AF:

0.454

Gnomad4 FIN exome

AF:

0.333

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.393

GnomAD4 genome

AF:

0.395

AC:

59972

AN:

152010

Hom.:

12141

Cov.:

AF XY:

0.394

AC XY:

29263

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.431

Gnomad4 AMR

AF:

0.368

Gnomad4 ASJ

AF:

0.429

Gnomad4 EAS

AF:

0.568

Gnomad4 SAS

AF:

0.462

Gnomad4 FIN

AF:

0.318

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.415

Alfa

AF:

0.354

Hom.:

4242

Bravo

AF:

0.397

EpiCase

AF:

0.375

EpiControl

AF:

0.387

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Glanzmann thrombasthenia

Benign:2

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. -
Benign, reviewed by expert panel	curation	ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	Sep 04, 2020	The ITGB3 synonymous variant NM_000212.2:c.1143A>C is very common in control population databases, with an overall allele frequency of 0.38777 in gnomAD v2.1.1. Note that initial reports of variation at this nucleotide position referred to the current reference allele as the variant at this position (c.1143C>A; PMID: 8878424, PMID: 20020534, and PMID: 25728920), however this reported "variant" is now considered the reference allele. In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.3

DANN

Benign

0.57

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