rs15908

Variant names:

• chr17-47290971-A-C
• rs15908
• NM_000212.3:c.1143A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-47290971-A-C
• chr17-47290971-A-G
• chr17-47290971-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Clinical Significance: Benign reviewed by expert panel B:8
• Conservation: PhyloP100: -0.320
• Publications: 33 publications found

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]

ENSG00000259753 (HGNC:):

EFCAB13-DT (HGNC:55338): (EFCAB13 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3	c.1143A>C	p.Val381Val	synonymous_variant	Exon 9 of 15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7	c.1143A>C	p.Val381Val	synonymous_variant	Exon 9 of 15	1	NM_000212.3	ENSP00000452786.2
ENSG00000259753	ENST00000560629.1	n.1107A>C		non_coding_transcript_exon_variant	Exon 9 of 18	2		ENSP00000456711.2

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59904 AN: 151892 Hom.: 12119 Cov.: 31

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

GnomAD2 exomes AF: 0.387 AC: 97372 AN: 251452 AF XY: 0.392

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 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.: 38 AF XY: 0.373 AC XY: 271008 AN XY: 727032

African (AFR) AF: 0.440 AC: 14722 AN: 33474

American (AMR) AF: 0.297 AC: 13294 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 11168 AN: 26130

East Asian (EAS) AF: 0.559 AC: 22177 AN: 39696

South Asian (SAS) AF: 0.454 AC: 39136 AN: 86244

European-Finnish (FIN) AF: 0.333 AC: 17785 AN: 53386

Middle Eastern (MID) AF: 0.473 AC: 2727 AN: 5766

European-Non Finnish (NFE) AF: 0.357 AC: 396346 AN: 1111632

Other (OTH) AF: 0.393 AC: 23701 AN: 60382

GnomAD4 genome AF: 0.395 AC: 59972 AN: 152010 Hom.: 12141 Cov.: 31 AF XY: 0.394 AC XY: 29263 AN XY: 74318

African (AFR) AF: 0.431 AC: 17873 AN: 41424

American (AMR) AF: 0.368 AC: 5625 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1490 AN: 3470

East Asian (EAS) AF: 0.568 AC: 2939 AN: 5174

South Asian (SAS) AF: 0.462 AC: 2225 AN: 4820

European-Finnish (FIN) AF: 0.318 AC: 3365 AN: 10580

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25061 AN: 67952

Other (OTH) AF: 0.415 AC: 876 AN: 2110

Alfa AF: 0.371 Hom.: 5710

Bravo AF: 0.397

EpiCase AF: 0.375

EpiControl AF: 0.387

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: reviewed by expert panel

Submissions by phenotype

not specified Benign:3

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Glanzmann thrombasthenia Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Sep 04, 2020

ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: curation

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
PhyloP100		-0.32
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs15908; hg19: chr17-45368337; COSMIC: COSV107525056; COSMIC: COSV107525056;