rs3768777

Positions:

• chr2-186591394-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.79).
• 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/exons	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.185+871A>G		intron_variant		ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.185+871A>G		intron_variant			NP_001138472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.185+871A>G		intron_variant		1	NM_002210.5	ENSP00000261023	P2

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

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.643

Alfa AF: 0.663 Hom.: 34760

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

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: rs3768777; hg19: chr2-187456121;