rs10174098

chr2-186628015-G-Achr2-186628015-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002210.5(ITGAV):c.523+2428G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,840 control chromosomes in the GnomAD database, including 30,004 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (30004 hom., cov: 31)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGAV	NM_002210.5	c.523+2428G>A		intron_variant		ENST00000261023.8
ITGAV	NM_001144999.3	c.385+2428G>A		intron_variant
ITGAV	NM_001145000.3	c.523+2428G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAV	ENST00000261023.8	c.523+2428G>A		intron_variant		1	NM_002210.5	P2

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94664 AN: 151722 Hom.: 29998 Cov.: 31

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.634

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.624 AC: 94700 AN: 151840 Hom.: 30004 Cov.: 31 AF XY: 0.623 AC XY: 46265 AN XY: 74224

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.629

Alfa AF: 0.623 Hom.: 9447

Bravo AF: 0.617

Asia WGS AF: 0.679 AC: 2361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.7
Dann	Benign	0.79

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

Other links and lift over

dbSNP: rs10174098; hg19: chr2-187492742;