Genetic Variant ITGB3:c.2015-85T>C (chr17-47302636-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000212.3(ITGB3):c.2015-85T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,529,136 control chromosomes in the GnomAD database, including 369,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38726 hom., cov: 32)

Exomes 𝑓: 0.69 ( 330679 hom. )

Consequence

ITGB3
NM_000212.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00500

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:

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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=-0.89).

BP6

Variant 17-47302636-T-C is Benign according to our data. Variant chr17-47302636-T-C is described in ClinVar as [Benign]. Clinvar id is 1271035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3 link	c.2015-85T>C		intron_variant	Intron 12 of 14	ENST00000559488.7	NP_000203.2	P05106-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGB3	ENST00000559488.7 link	c.2015-85T>C	intron_variant	Intron 12 of 14	1	NM_000212.3	ENSP00000452786.2	P05106-1
ENSG00000259753	ENST00000560629.1 link	n.1979-85T>C	intron_variant	Intron 12 of 17	2		ENSP00000456711.2	H3BM21
ITGB3	ENST00000696963.1 link	c.2015-85T>C	intron_variant	Intron 12 of 13			ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes

AF:

0.711

AC:

108015

AN:

151980

Hom.:

38701

Cov.:

show subpopulations

Gnomad AFR

AF:

0.770

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.634

Gnomad ASJ

AF:

0.723

Gnomad EAS

AF:

0.815

Gnomad SAS

AF:

0.732

Gnomad FIN

AF:

0.667

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.710

GnomAD4 exome

AF:

0.692

AC:

952798

AN:

1377038

Hom.:

330679

AF XY:

0.694

AC XY:

478453

AN XY:

689414

show subpopulations

Gnomad4 AFR exome

AF:

0.769

Gnomad4 AMR exome

AF:

0.559

Gnomad4 ASJ exome

AF:

0.698

Gnomad4 EAS exome

AF:

0.831

Gnomad4 SAS exome

AF:

0.742

Gnomad4 FIN exome

AF:

0.668

Gnomad4 NFE exome

AF:

0.686

Gnomad4 OTH exome

AF:

0.710

GnomAD4 genome

AF:

0.711

AC:

108091

AN:

152098

Hom.:

38726

Cov.:

AF XY:

0.708

AC XY:

52630

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.770

Gnomad4 AMR

AF:

0.634

Gnomad4 ASJ

AF:

0.723

Gnomad4 EAS

AF:

0.815

Gnomad4 SAS

AF:

0.733

Gnomad4 FIN

AF:

0.667

Gnomad4 NFE

AF:

0.688

Gnomad4 OTH

AF:

0.707

Alfa

AF:

0.682

Hom.:

13899

Bravo

AF:

0.711

Asia WGS

AF:

0.735

AC:

2555

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.4

DANN

Benign

0.45

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