rs115600591

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BA1BP4

This summary comes from the ClinGen Evidence Repository: The c.40G>A; p.Val14Met missense variant has not been reported in the literature to our knowledge. It is present in an African population at an allele frequency of 0.03606. Computational evidence suggests no impact on the gene or gene product with a REVEL score of 0.115. In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1 and BP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA8622831/MONDO:0010119/011

Frequency

Genomes: 𝑓 0.010 ( 24 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 27 hom. )

Consequence

ITGB3
NM_000212.3 missense

Scores

Clinical Significance

Benign reviewed by expert panel B:5

Conservation

PhyloP100: 0.0650

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

Glanzmann thrombasthenia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Glanzmann thrombasthenia 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
bleeding disorder, platelet-type, 24
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
platelet-type bleeding disorder 16
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
autosomal dominant macrothrombocytopenia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Glanzmann's thrombasthenia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ITGB3 links:

ENSG00000259753 (HGNC:):

ENSG00000259753 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

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 link	c.40G>A	p.Val14Met	missense_variant	Exon 1 of 15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ITGB3	ENST00000559488.7 link	c.40G>A	p.Val14Met	missense_variant	Exon 1 of 15	1	NM_000212.3	ENSP00000452786.2
ITGB3	ENST00000571680.1 link	c.40G>A	p.Val14Met	missense_variant	Exon 1 of 9	1		ENSP00000461626.1
ENSG00000259753	ENST00000560629.1 link	n.4G>A		non_coding_transcript_exon_variant	Exon 1 of 18	2		ENSP00000456711.2
ITGB3	ENST00000696963.1 link	c.40G>A	p.Val14Met	missense_variant	Exon 1 of 14			ENSP00000513002.1

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1561

AN:

151838

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00479

GnomAD2 exomes

AF:

0.000841

AC:

AN:

73718

AF XY:

0.000696

show subpopulations

Gnomad AFR exome

AF:

0.0341

Gnomad AMR exome

AF:

0.000710

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000244

Gnomad OTH exome

AF:

0.000986

GnomAD4 exome

AF:

0.00100

AC:

1247

AN:

1242408

Hom.:

Cov.:

AF XY:

0.000881

AC XY:

538

AN XY:

610550

show subpopulations

African (AFR)

AF:

0.0397

AC:

1024

AN:

25778

American (AMR)

AF:

0.000838

AC:

AN:

22684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20998

East Asian (EAS)

AF:

0.00

AC:

AN:

27396

South Asian (SAS)

AF:

0.000134

AC:

AN:

59840

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31864

Middle Eastern (MID)

AF:

0.00429

AC:

AN:

3726

European-Non Finnish (NFE)

AF:

0.0000840

AC:

AN:

1000266

Other (OTH)

AF:

0.00193

AC:

AN:

49856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

113

169

226

282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0103

AC:

1559

AN:

151946

Hom.:

Cov.:

AF XY:

0.00999

AC XY:

742

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0361

AC:

1498

AN:

41504

American (AMR)

AF:

0.00249

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10494

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000177

AC:

AN:

67916

Other (OTH)

AF:

0.00474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

147

221

294

368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00654

Hom.:

Bravo

AF:

0.0118

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0207

AC:

ESP6500EA

AF:

0.000429

AC:

ExAC

AF:

0.00170

AC:

168

Asia WGS

AF:

0.00203

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 25, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely 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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glanzmann thrombasthenia

Benign:2

Jan 12, 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. -

Jun 04, 2020

ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

The c.40G>A; p.Val14Met missense variant has not been reported in the literature to our knowledge. It is present in an African population at an allele frequency of 0.03606. Computational evidence suggests no impact on the gene or gene product with a REVEL score of 0.115. In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1 and BP4. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.32

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

PhyloP100

0.065

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.46

N;.

Sift

Uncertain

0.028

D;.

Sift4G

Uncertain

0.042

D;D

Polyphen

0.026

B;.

Vest4

0.23

MVP

0.66

MPC

0.42

ClinPred

0.013

GERP RS

-2.7

PromoterAI

0.026

Neutral

(source)

Varity_R

0.062

gMVP

0.48

Mutation Taster

=299/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over