rs3795865

chr2-186635955-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.632-127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 682,032 control chromosomes in the GnomAD database, including 37,244 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 0.28 (6832 hom., cov: 32)
  • Exomes 𝑓: 0.33 (30412 hom.)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGAV	NM_002210.5	c.632-127A>G		intron_variant		ENST00000261023.8
ITGAV	NM_001144999.3	c.494-127A>G		intron_variant
ITGAV	NM_001145000.3	c.524-127A>G		intron_variant
ITGAV	XM_047444225.1	c.-212-127A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAV	ENST00000261023.8	c.632-127A>G		intron_variant		1	NM_002210.5	P2

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43203 AN: 151974 Hom.: 6834 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.329 AC: 174538 AN: 529940 Hom.: 30412 AF XY: 0.331 AC XY: 91567 AN XY: 276834

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.0867

Gnomad4 SAS exome AF: 0.324

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.362

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.284 AC: 43199 AN: 152092 Hom.: 6832 Cov.: 32 AF XY: 0.281 AC XY: 20865 AN XY: 74354

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.0774

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.298

Alfa AF: 0.292 Hom.: 1002

Bravo AF: 0.275

Asia WGS AF: 0.215 AC: 747 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.3
Dann	Benign	0.62

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: rs3795865; hg19: chr2-187500682;