Variant 2-186622433-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_002210.5(ITGAV):c.408+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 1,591,498 control chromosomes in the GnomAD database, including 444,592 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.75 ( 43295 hom., cov: 31)

Exomes 𝑓: 0.75 ( 401297 hom. )

Consequence

ITGAV
NM_002210.5 splice_region, intron

Scores

Splicing: ADA: 0.00002264

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

ITGAV (HGNC:6150): (integrin subunit alpha V) The product of this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha subunit and a beta subunit that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha V subunit. This subunit associates with beta 1, beta 3, beta 5, beta 6 and beta 8 subunits. The heterodimer consisting of alpha V and beta 3 subunits is also known as the vitronectin receptor. This integrin may regulate angiogenesis and cancer progression. Alternative splicing results in multiple transcript variants. Note that the integrin alpha 5 and integrin alpha V subunits are encoded by distinct genes. [provided by RefSeq, Oct 2015]

ITGAV links:

ITGAV (HGNC:):

ITGAV links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ITGAV	NM_002210.5 linkuse as main transcript	c.408+3G>A	splice_region_variant, intron_variant	ENST00000261023.8	NP_002201.2	P06756-1L7RXH0
ITGAV	NM_001145000.3 linkuse as main transcript	c.408+3G>A	splice_region_variant, intron_variant		NP_001138472.2	P06756-2
ITGAV	NM_001144999.3 linkuse as main transcript	c.270+3G>A	splice_region_variant, intron_variant		NP_001138471.2	P06756-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8 linkuse as main transcript	c.408+3G>A		splice_region_variant, intron_variant		1	NM_002210.5	ENSP00000261023.3		P06756-1

Frequencies

GnomAD3 genomes

AF:

0.754

AC:

114643

AN:

151950

Hom.:

43258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.775

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.737

Gnomad ASJ

AF:

0.714

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.740

Gnomad FIN

AF:

0.750

Gnomad MID

AF:

0.668

Gnomad NFE

AF:

0.742

Gnomad OTH

AF:

0.754

GnomAD3 exomes

AF:

0.746

AC:

187310

AN:

251098

Hom.:

70118

AF XY:

0.746

AC XY:

101302

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.773

Gnomad AMR exome

AF:

0.712

Gnomad ASJ exome

AF:

0.730

Gnomad EAS exome

AF:

0.857

Gnomad SAS exome

AF:

0.737

Gnomad FIN exome

AF:

0.752

Gnomad NFE exome

AF:

0.737

Gnomad OTH exome

AF:

0.746

GnomAD4 exome

AF:

0.746

AC:

1073721

AN:

1439430

Hom.:

401297

Cov.:

AF XY:

0.745

AC XY:

534642

AN XY:

717604

show subpopulations

Gnomad4 AFR exome

AF:

0.770

Gnomad4 AMR exome

AF:

0.718

Gnomad4 ASJ exome

AF:

0.730

Gnomad4 EAS exome

AF:

0.861

Gnomad4 SAS exome

AF:

0.737

Gnomad4 FIN exome

AF:

0.747

Gnomad4 NFE exome

AF:

0.743

Gnomad4 OTH exome

AF:

0.755

GnomAD4 genome

AF:

0.755

AC:

114739

AN:

152068

Hom.:

43295

Cov.:

AF XY:

0.754

AC XY:

56022

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.775

Gnomad4 AMR

AF:

0.737

Gnomad4 ASJ

AF:

0.714

Gnomad4 EAS

AF:

0.853

Gnomad4 SAS

AF:

0.742

Gnomad4 FIN

AF:

0.750

Gnomad4 NFE

AF:

0.742

Gnomad4 OTH

AF:

0.751

Alfa

AF:

0.743

Hom.:

24926

Bravo

AF:

0.755

Asia WGS

AF:

0.781

AC:

2717

AN:

3478

EpiCase

AF:

0.735

EpiControl

AF:

0.732

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000023

dbscSNV1_RF

Benign

0.0040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over