chr2-186605617-G-C

Variant names:

• chr2-186605617-G-C
• rs3911238
• NM_002210.5:c.316+3466G>C

Variant summary

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

The NM_002210.5(ITGAV):​c.316+3466G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 151,682 control chromosomes in the GnomAD database, including 5,613 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 0.23 (5613 hom., cov: 31)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 16 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.316+3466G>C		intron_variant	Intron 2 of 29	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.316+3466G>C		intron_variant	Intron 2 of 27		NP_001138472.2
ITGAV	NM_001144999.3	c.178+3466G>C		intron_variant	Intron 2 of 29		NP_001138471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.316+3466G>C		intron_variant	Intron 2 of 29	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35284 AN: 151566 Hom.: 5613 Cov.: 31

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.233 AC: 35283 AN: 151682 Hom.: 5613 Cov.: 31 AF XY: 0.243 AC XY: 18040 AN XY: 74094

African (AFR) AF: 0.0544 AC: 2253 AN: 41382

American (AMR) AF: 0.311 AC: 4732 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3468

East Asian (EAS) AF: 0.728 AC: 3758 AN: 5164

South Asian (SAS) AF: 0.269 AC: 1296 AN: 4810

European-Finnish (FIN) AF: 0.392 AC: 4078 AN: 10412

Middle Eastern (MID) AF: 0.197 AC: 57 AN: 290

European-Non Finnish (NFE) AF: 0.260 AC: 17651 AN: 67920

Other (OTH) AF: 0.227 AC: 480 AN: 2110

Alfa AF: 0.242 Hom.: 636

Bravo AF: 0.221

Asia WGS AF: 0.437 AC: 1521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.33
PhyloP100		0.050
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: rs3911238; hg19: chr2-187470344;