rs2887827

chr2-186606754-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.316+4603G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,750 control chromosomes in the GnomAD database, including 4,284 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 0.24 (4284 hom., cov: 31)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGAV	NM_002210.5	c.316+4603G>C		intron_variant		ENST00000261023.8
ITGAV	NM_001144999.3	c.178+4603G>C		intron_variant
ITGAV	NM_001145000.3	c.316+4603G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAV	ENST00000261023.8	c.316+4603G>C		intron_variant		1	NM_002210.5	P2

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35845 AN: 151632 Hom.: 4285 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.236 AC: 35860 AN: 151750 Hom.: 4284 Cov.: 31 AF XY: 0.238 AC XY: 17611 AN XY: 74124

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.236

Alfa AF: 0.255 Hom.: 599

Bravo AF: 0.234

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.0
Dann	Benign	0.63

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: rs2887827; hg19: chr2-187471481;