17-47287192-T-C

Position:

chr17-47287192-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP7BS1BP4

This summary comes from the ClinGen Evidence Repository: The NM_000212.2(ITGB3):c.900T>C (p.His300=) synonymous variant was observed by Illumina as part of a predisposition screen in an ostensibly healthy population but has not been reported in a GT patient. It is not predicted to have an impact on splicing. The variant occurs at an allele frequency greater than expected for the disorder with a MAF of 0.003664 (38/10370 alleles) in the gnomAD Ashkenazi Jewish population.In summary, this variant meets criteria to be classified as Likely Benign for GT. GT-specific criteria applied: BS1, BP4, and BP7 LINK:https://erepo.genome.network/evrepo/ui/classification/CA8623076/MONDO:0010119/011

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

ITGB3
NM_000212.3 synonymous

Scores

Clinical Significance

Likely benign reviewed by expert panel U:1B:5

Conservation

PhyloP100: 0.165

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 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.

BS1

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.900T>C	p.His300=	synonymous_variant	6/15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7 linkuse as main transcript	c.900T>C	p.His300=	synonymous_variant	6/15	1	NM_000212.3	ENSP00000452786	P1	P05106-1
ITGB3	ENST00000571680.1 linkuse as main transcript	c.900T>C	p.His300=	synonymous_variant	6/9	1		ENSP00000461626
ITGB3	ENST00000696963.1 linkuse as main transcript	c.900T>C	p.His300=	synonymous_variant	6/14			ENSP00000513002		P05106-2

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000251

AC:

AN:

251204

Hom.:

AF XY:

0.000250

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000159

AC:

233

AN:

1461662

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

121

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00310

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000197

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000212

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:5

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Glanzmann thrombasthenia

Uncertain:1Benign:1

Likely benign, reviewed by expert panel	curation	ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	May 07, 2021	The NM_000212.2(ITGB3):c.900T>C (p.His300=) synonymous variant was observed by Illumina as part of a predisposition screen in an ostensibly healthy population but has not been reported in a GT patient. It is not predicted to have an impact on splicing. The variant occurs at an allele frequency greater than expected for the disorder with a MAF of 0.003664 (38/10370 alleles) in the gnomAD Ashkenazi Jewish population.In summary, this variant meets criteria to be classified as Likely Benign for GT. GT-specific criteria applied: BS1, BP4, and BP7 -
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 07, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 05, 2017	- -

ITGB3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 26, 2019

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.1

DANN

Benign

0.80

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