dbSNP rs5917: ITGB3:p.Arg169Gln (chr17-47284587-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BS3BA1

This summary comes from the ClinGen Evidence Repository: The c.506G>A (p.Arg169Gln) missense variant has been reported in the literature many times as the Penb antigenic epitope. However, this polymorphism has not been reported in association with Glanzmann thrombasthenia. It is present in a Latino control population at an allele frequency of 0.01439 and functional studies in CHO cells have shown no deleterious effect on surface expression or fibrinogen binding. In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1, BS3. LINK:https://erepo.genome.network/evrepo/ui/classification/CA123232/MONDO:0010119/011

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00067 ( 8 hom. )

Consequence

ITGB3
NM_000212.3 missense

Scores

Clinical Significance

Benign reviewed by expert panel B:6

Conservation

PhyloP100: 2.52

Publications

12 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 links:

ENSG00000259753 (HGNC:):

ENSG00000259753 links:

EFCAB13-DT (HGNC:55338): (EFCAB13 divergent transcript)

EFCAB13-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BS3

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.506G>A	p.Arg169Gln	missense	Exon 4 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.506G>A	p.Arg169Gln	missense	Exon 4 of 15	ENSP00000452786.2	P05106-1
ITGB3	ENST00000571680.1	TSL:1	c.506G>A	p.Arg169Gln	missense	Exon 4 of 9	ENSP00000461626.1	I3L4X8
ENSG00000259753	ENST00000560629.1	TSL:2	n.470G>A		non_coding_transcript_exon	Exon 4 of 18	ENSP00000456711.2	H3BM21

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

156

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00701

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00229

AC:

576

AN:

251474

AF XY:

0.00160

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00277

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000672

AC:

982

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000569

AC XY:

414

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33480

American (AMR)

AF:

0.0127

AC:

568

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00705

AC:

280

AN:

39700

South Asian (SAS)

AF:

0.000406

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000495

AC:

AN:

1112012

Other (OTH)

AF:

0.000447

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

144

215

287

359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00103

AC:

157

AN:

152226

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.000458

AC:

AN:

41526

American (AMR)

AF:

0.00706

AC:

108

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00309

AC:

AN:

5178

South Asian (SAS)

AF:

0.00104

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68012

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000881

Hom.:

Bravo

AF:

0.00152

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00194

AC:

235

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glanzmann thrombasthenia (2)

not provided (2)

not specified (1)

PEN(a)/PEN(b) ALLOANTIGEN POLYMORPHISM (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.53

Eigen

Benign

-0.025

Eigen_PC

Benign

0.055

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0098

MetaSVM

Uncertain

0.025

MutationAssessor

Benign

1.2

PhyloP100

2.5

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.94

Sift

Benign

0.15

Sift4G

Benign

0.67

Polyphen

0.92

Vest4

0.34

MVP

0.94

MPC

0.93

ClinPred

0.020

GERP RS

4.9

Varity_R

0.18

gMVP

0.47

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over