2-186678500-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.*1208G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 235,578 control chromosomes in the GnomAD database, including 6,494 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 0.22 (4076 hom., cov: 33)
  • Exomes 𝑓: 0.23 (2418 hom.)
• Consequence: ITGAV NM_002210.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGAV	NM_002210.5	c.*1208G>C		3_prime_UTR_variant	30/30	ENST00000261023.8
ITGAV	NM_001144999.3	c.*1208G>C		3_prime_UTR_variant	30/30
ITGAV	NM_001145000.3	c.*1208G>C		3_prime_UTR_variant	28/28
ITGAV	XM_047444225.1	c.*1208G>C		3_prime_UTR_variant	26/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAV	ENST00000261023.8	c.*1208G>C		3_prime_UTR_variant	30/30	1	NM_002210.5	P2
	ENST00000453665.1	n.131+16657C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33883 AN: 151842 Hom.: 4074 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.230 AC: 19209 AN: 83618 Hom.: 2418 Cov.: 0 AF XY: 0.225 AC XY: 10393 AN XY: 46122

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.194

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.0714

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.223 AC: 33886 AN: 151960 Hom.: 4076 Cov.: 33 AF XY: 0.220 AC XY: 16330 AN XY: 74282

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0772

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.242

Alfa AF: 0.143 Hom.: 282

Bravo AF: 0.220

Asia WGS AF: 0.173 AC: 600 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.66
Dann	Benign	0.51

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: rs11902171; hg19: chr2-187543227;