chr17-47253877-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000212.3(ITGB3):c.16C>T(p.Arg6Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,253,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

ITGB3
NM_000212.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.0240

Publications

1 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04896894).

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.16C>T	p.Arg6Trp	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.16C>T	p.Arg6Trp	missense	Exon 1 of 15	ENSP00000452786.2	P05106-1
ITGB3	ENST00000571680.1	TSL:1	c.16C>T	p.Arg6Trp	missense	Exon 1 of 9	ENSP00000461626.1	I3L4X8
ITGB3	ENST00000696963.1		c.16C>T	p.Arg6Trp	missense	Exon 1 of 14	ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes

AF:

0.0000726

AC:

AN:

151560

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

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

GnomAD2 exomes

AF:

0.000244

AC:

AN:

16392

AF XY:

0.000186

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000540

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000535

AC:

AN:

1102346

Hom.:

Cov.:

AF XY:

0.0000493

AC XY:

AN XY:

527552

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22794

American (AMR)

AF:

0.00

AC:

AN:

9354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15170

East Asian (EAS)

AF:

0.00

AC:

AN:

26038

South Asian (SAS)

AF:

0.00

AC:

AN:

26526

European-Finnish (FIN)

AF:

0.0000853

AC:

AN:

23438

Middle Eastern (MID)

AF:

0.000327

AC:

AN:

3056

European-Non Finnish (NFE)

AF:

0.0000569

AC:

AN:

932038

Other (OTH)

AF:

0.0000683

AC:

AN:

43932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000726

AC:

AN:

151560

Hom.:

Cov.:

AF XY:

0.0000810

AC XY:

AN XY:

74036

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41282

American (AMR)

AF:

0.00

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67868

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.566

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:

0.000486

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000138

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glanzmann thrombasthenia (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.27

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.64

M_CAP

Benign

0.026

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.024

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.0

Sift

Benign

0.067

Sift4G

Benign

0.079

Polyphen

0.0

Vest4

0.19

MutPred

0.40

Loss of disorder (P = 0.0101)

MVP

0.69

MPC

0.42

ClinPred

0.034

GERP RS

-2.0

PromoterAI

-0.20

Neutral

(source)

Varity_R

0.066

gMVP

0.66

Mutation Taster

=99/1

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