rs5920

Positions:

• chr17-47283530-T-C
• chr17-47283530-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP7 BA1 BP4

This summary comes from the ClinGen Evidence Repository: The NM_000212.2:c.342T>C variant, which leads to a synonymous change, Ile114Ile, is reported at a high frequency in the African population in gnomAD and ExAC (0.05). In-silico splicing predictors do not predict splicing impact. PMID:27469266 reports on this and other polymorphic, non-causal variants found in linkage disequilibrium with deleterious mutations in GT patients. Ile114Ile is classified as a benign variant. GT-specific criteria applied: BA1, BP4, and BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA8622916/MONDO:0010119/011

• Frequency:
  • Genomes: 𝑓 0.016 (90 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (52 hom.)
• Consequence: ITGB3 NM_000212.3 synonymous
• Clinical Significance: Benign reviewed by expert panel B:4
• Conservation: PhyloP100: -0.560

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB3	NM_000212.3	c.342T>C	p.Ile114=	synonymous_variant	3/15	ENST00000559488.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB3	ENST00000559488.7	c.342T>C	p.Ile114=	synonymous_variant	3/15	1	NM_000212.3	P1
ITGB3	ENST00000571680.1	c.342T>C	p.Ile114=	synonymous_variant	3/9	1
ITGB3	ENST00000696963.1	c.342T>C	p.Ile114=	synonymous_variant	3/14

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2446 AN: 152184 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00441 AC: 1105 AN: 250394 Hom.: 20 AF XY: 0.00336 AC XY: 455 AN XY: 135430

Gnomad AFR exome AF: 0.0545

Gnomad AMR exome AF: 0.00465

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000311

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00173 AC: 2524 AN: 1461892 Hom.: 52 Cov.: 33 AF XY: 0.00149 AC XY: 1082 AN XY: 727248

Gnomad4 AFR exome AF: 0.0538

Gnomad4 AMR exome AF: 0.00503

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000158

Gnomad4 OTH exome AF: 0.00427

GnomAD4 genome AF: 0.0163 AC: 2475 AN: 152302 Hom.: 90 Cov.: 32 AF XY: 0.0154 AC XY: 1145 AN XY: 74466

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.00993

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00718 Hom.: 22

Bravo AF: 0.0185

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: reviewed by expert panel

Submissions by phenotype

Glanzmann thrombasthenia Benign:2

Benign, reviewed by expert panel	curation	ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	May 07, 2021	The NM_000212.2:c.342T>C variant, which leads to a synonymous change, Ile114Ile, is reported at a high frequency in the African population in gnomAD and ExAC (0.05). In-silico splicing predictors do not predict splicing impact. PMID: 27469266 reports on this and other polymorphic, non-causal variants found in linkage disequilibrium with deleterious mutations in GT patients. Ile114Ile is classified as a benign variant. GT-specific criteria applied: BA1, BP4, and BP7. -
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

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.0
DANN	Benign	0.76

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

Other links and lift over

dbSNP: rs5920; hg19: chr17-45360896; COSMIC: COSV99068316; COSMIC: COSV99068316;