rs3768777

Variant names:

• chr2-186591394-A-G
• rs3768777
• NM_002210.5:c.185+871A>G

Variant summary

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

The NM_002210.5(ITGAV):​c.185+871A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,892 control chromosomes in the GnomAD database, including 31,256 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 0.64 (31256 hom., cov: 31)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 12 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=-0.79).
• 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 rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.185+871A>G		intron_variant	Intron 1 of 29	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.185+871A>G		intron_variant	Intron 1 of 27		NP_001138472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.185+871A>G		intron_variant	Intron 1 of 29	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96935 AN: 151774 Hom.: 31246 Cov.: 31

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.638 AC: 96982 AN: 151892 Hom.: 31256 Cov.: 31 AF XY: 0.638 AC XY: 47328 AN XY: 74224

African (AFR) AF: 0.540 AC: 22354 AN: 41366

American (AMR) AF: 0.640 AC: 9775 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2280 AN: 3470

East Asian (EAS) AF: 0.798 AC: 4133 AN: 5176

South Asian (SAS) AF: 0.630 AC: 3026 AN: 4804

European-Finnish (FIN) AF: 0.665 AC: 7005 AN: 10540

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46182 AN: 67956

Other (OTH) AF: 0.643 AC: 1355 AN: 2106

Alfa AF: 0.663 Hom.: 40904

Bravo AF: 0.633

Asia WGS AF: 0.682 AC: 2372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.0
DANN	Benign	0.73
PhyloP100		-0.19
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: rs3768777; hg19: chr2-187456121;