Variant chr17-47253855-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
ITGB3	NM_000212.3 linkuse as main transcript	c.-7G>C		5_prime_UTR_variant	1/15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7 linkuse as main transcript	c.-7G>C	5_prime_UTR_variant	1/15	1	NM_000212.3	ENSP00000452786	P1	P05106-1
ITGB3	ENST00000571680.1 linkuse as main transcript	c.-7G>C	5_prime_UTR_variant	1/9	1		ENSP00000461626
ITGB3	ENST00000696963.1 linkuse as main transcript	c.-7G>C	5_prime_UTR_variant	1/14			ENSP00000513002		P05106-2

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

GnomAD3 exomes

AF:

0.0345

AC:

AN:

2262

Hom.:

AF XY:

0.0322

AC XY:

AN XY:

1614

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 SAS exome

AF:

0.110

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

Gnomad4 AFR exome

AF:

0.00483

Gnomad4 AMR exome

AF:

0.0182

Gnomad4 ASJ exome

AF:

0.0302

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.0891

Gnomad4 FIN exome

AF:

0.0329

Gnomad4 NFE exome

AF:

0.0229

Gnomad4 OTH exome

AF:

0.0417

GnomAD4 genome

AF:

0.0291

AC:

4411

AN:

151678

Hom.:

211

Cov.:

AF XY:

0.0318

AC XY:

2356

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.00637

Gnomad4 AMR

AF:

0.0242

Gnomad4 ASJ

AF:

0.0358

Gnomad4 EAS

AF:

0.226

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.0273

Gnomad4 NFE

AF:

0.0244

Gnomad4 OTH

AF:

0.0318

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

Glanzmann thrombasthenia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.88

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over