17-47253855-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000212.3(ITGB3):c.-7G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 1,219,630 control chromosomes in the GnomAD database, including 1,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 211 hom., cov: 32)

Exomes 𝑓: 0.029 ( 945 hom. )

Consequence

ITGB3
NM_000212.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.331

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 17-47253855-G-C is Benign according to our data. Variant chr17-47253855-G-C is described in ClinVar as Benign. ClinVar VariationId is 255534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3 link	c.-7G>C		5_prime_UTR_variant	Exon 1 of 15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ITGB3	ENST00000559488.7 link	c.-7G>C	5_prime_UTR_variant	Exon 1 of 15	1	NM_000212.3	ENSP00000452786.2
ITGB3	ENST00000571680.1 link	c.-7G>C	5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000461626.1
ITGB3	ENST00000696963.1 link	c.-7G>C	5_prime_UTR_variant	Exon 1 of 14			ENSP00000513002.1
ENSG00000259753	ENST00000560629.1 link	n.-43G>C	upstream_gene_variant		2		ENSP00000456711.2

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4414

AN:

151572

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00638

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0243

Gnomad ASJ

AF:

0.0358

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.0243

Gnomad OTH

AF:

0.0326

GnomAD2 exomes

AF:

0.0345

AC:

AN:

2262

AF XY:

0.0322

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0217

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.0278

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0290

AC:

30954

AN:

1067952

Hom.:

945

Cov.:

AF XY:

0.0292

AC XY:

14799

AN XY:

506386

show subpopulations

African (AFR)

AF:

0.00483

AC:

107

AN:

22166

American (AMR)

AF:

0.0182

AC:

143

AN:

7870

Ashkenazi Jewish (ASJ)

AF:

0.0302

AC:

406

AN:

13432

East Asian (EAS)

AF:

0.200

AC:

4998

AN:

25030

South Asian (SAS)

AF:

0.0891

AC:

1819

AN:

20412

European-Finnish (FIN)

AF:

0.0329

AC:

708

AN:

21526

Middle Eastern (MID)

AF:

0.0322

AC:

AN:

2886

European-Non Finnish (NFE)

AF:

0.0229

AC:

20915

AN:

912266

Other (OTH)

AF:

0.0417

AC:

1765

AN:

42364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

1265

2530

3794

5059

6324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

976

1952

2928

3904

4880

<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:

0.0291

AC:

4411

AN:

151678

Hom.:

211

Cov.:

AF XY:

0.0318

AC XY:

2356

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.00637

AC:

264

AN:

41468

American (AMR)

AF:

0.0242

AC:

368

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.0358

AC:

124

AN:

3464

East Asian (EAS)

AF:

0.226

AC:

1155

AN:

5102

South Asian (SAS)

AF:

0.101

AC:

487

AN:

4826

European-Finnish (FIN)

AF:

0.0273

AC:

285

AN:

10436

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0244

AC:

1653

AN:

67838

Other (OTH)

AF:

0.0318

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

197

394

590

787

984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0237

Hom.:

Bravo

AF:

0.0282

Asia WGS

AF:

0.138

AC:

476

AN:

3444

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Glanzmann thrombasthenia

Benign:1

Jan 13, 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.

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.33

PromoterAI

0.0054

Neutral

(source)

Mutation Taster

=297/3

polymorphism (auto)

(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