rs10171481

Variant names:

• chr2-186627733-G-A
• rs10171481
• NM_002210.5:c.523+2146G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002210.5(ITGAV):​c.523+2146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 152,006 control chromosomes in the GnomAD database, including 43,064 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 0.75 (43064 hom., cov: 31)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002210.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAV	NM_002210.5	MANE Select	c.523+2146G>A		intron	N/A	NP_002201.2
	ITGAV	NM_001145000.3		c.523+2146G>A		intron	N/A	NP_001138472.2
	ITGAV	NM_001144999.3		c.385+2146G>A		intron	N/A	NP_001138471.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAV	ENST00000261023.8	TSL:1 MANE Select	c.523+2146G>A		intron	N/A	ENSP00000261023.3
	ITGAV	ENST00000374907.7	TSL:1	c.523+2146G>A		intron	N/A	ENSP00000364042.3
	ITGAV	ENST00000696906.1		c.523+2146G>A		intron	N/A	ENSP00000512967.1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114333 AN: 151888 Hom.: 43027 Cov.: 31

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.754

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

GnomAD4 genome AF: 0.753 AC: 114428 AN: 152006 Hom.: 43064 Cov.: 31 AF XY: 0.752 AC XY: 55889 AN XY: 74308

African (AFR) AF: 0.768 AC: 31833 AN: 41446

American (AMR) AF: 0.736 AC: 11246 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2474 AN: 3468

East Asian (EAS) AF: 0.852 AC: 4404 AN: 5168

South Asian (SAS) AF: 0.741 AC: 3565 AN: 4812

European-Finnish (FIN) AF: 0.751 AC: 7944 AN: 10576

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50448 AN: 67960

Other (OTH) AF: 0.751 AC: 1576 AN: 2098

Alfa AF: 0.740 Hom.: 16170

Bravo AF: 0.753

Asia WGS AF: 0.781 AC: 2714 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0030
DANN	Benign	0.58
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10171481; hg19: chr2-187492460;