rs5919

Variant names:

• chr17-47287174-T-C
• rs5919
• NM_000212.3:c.882T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP7 BP4 BA1

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
• Clinical Significance: Benign reviewed by expert panel B:6
• Conservation: PhyloP100: 1.03
• Publications: 26 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 -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 rank	MANE	Protein	UniProt
ITGB3	NM_000212.3	c.882T>C	p.Pro294Pro	synonymous_variant	Exon 6 of 15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7	c.882T>C	p.Pro294Pro	synonymous_variant	Exon 6 of 15	1	NM_000212.3	ENSP00000452786.2
ENSG00000259753	ENST00000560629.1	n.846T>C		non_coding_transcript_exon_variant	Exon 6 of 18	2		ENSP00000456711.2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15995 AN: 152084 Hom.: 1009 Cov.: 32

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

GnomAD2 exomes AF: 0.100 AC: 25242 AN: 251236 AF XY: 0.103

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 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.: 33 AF XY: 0.0827 AC XY: 60153 AN XY: 727118

African (AFR) AF: 0.157 AC: 5270 AN: 33468

American (AMR) AF: 0.0613 AC: 2743 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3611 AN: 26132

East Asian (EAS) AF: 0.221 AC: 8766 AN: 39698

South Asian (SAS) AF: 0.160 AC: 13761 AN: 86248

European-Finnish (FIN) AF: 0.0416 AC: 2223 AN: 53412

Middle Eastern (MID) AF: 0.173 AC: 997 AN: 5756

European-Non Finnish (NFE) AF: 0.0664 AC: 73850 AN: 1111824

Other (OTH) AF: 0.0996 AC: 6011 AN: 60372

GnomAD4 genome AF: 0.105 AC: 16029 AN: 152202 Hom.: 1018 Cov.: 32 AF XY: 0.105 AC XY: 7815 AN XY: 74414

African (AFR) AF: 0.157 AC: 6516 AN: 41506

American (AMR) AF: 0.0879 AC: 1345 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3466

East Asian (EAS) AF: 0.241 AC: 1242 AN: 5162

South Asian (SAS) AF: 0.167 AC: 806 AN: 4824

European-Finnish (FIN) AF: 0.0352 AC: 374 AN: 10622

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0708 AC: 4817 AN: 67998

Other (OTH) AF: 0.111 AC: 234 AN: 2116

Alfa AF: 0.0867 Hom.: 1224

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

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2018

GeneDx

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

- -

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. -

Dec 01, 2022

ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: curation

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. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		1.0
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5919; hg19: chr17-45364540; COSMIC: COSV71383340; COSMIC: COSV71383340;