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:6

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):

platelet-type bleeding disorder 16
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
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)
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

Specifications for ITGB3 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000212.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	NM_000212.3	MANE Select	c.40G>A	p.Val14Met	missense	Exon 1 of 15	NP_000203.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGB3	ENST00000559488.7	TSL:1 MANE Select	c.40G>A	p.Val14Met	missense	Exon 1 of 15	ENSP00000452786.2	P05106-1
ITGB3	ENST00000571680.1	TSL:1	c.40G>A	p.Val14Met	missense	Exon 1 of 9	ENSP00000461626.1	I3L4X8
ENSG00000259753	ENST00000560629.1	TSL:2	n.4G>A		non_coding_transcript_exon	Exon 1 of 18	ENSP00000456711.2	H3BM21

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

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Glanzmann thrombasthenia (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

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

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.065

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.46

Sift

Uncertain

0.028

Sift4G

Uncertain

0.042

Polyphen

0.026

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over