rs9333288

chr2-186622433-G-Achr2-186622433-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002210.5(ITGAV):c.408+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 1,591,498 control chromosomes in the GnomAD database, including 444,592 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 0.75 (43295 hom., cov: 31)
  • Exomes 𝑓: 0.75 (401297 hom.)
• Consequence: ITGAV NM_002210.5 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00002264
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGAV	NM_002210.5	c.408+3G>A		splice_donor_region_variant, intron_variant		ENST00000261023.8
ITGAV	NM_001144999.3	c.270+3G>A		splice_donor_region_variant, intron_variant
ITGAV	NM_001145000.3	c.408+3G>A		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAV	ENST00000261023.8	c.408+3G>A		splice_donor_region_variant, intron_variant		1	NM_002210.5	P2

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114643 AN: 151950 Hom.: 43258 Cov.: 31

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.754

GnomAD3 exomes AF: 0.746 AC: 187310 AN: 251098 Hom.: 70118 AF XY: 0.746 AC XY: 101302 AN XY: 135734

Gnomad AFR exome AF: 0.773

Gnomad AMR exome AF: 0.712

Gnomad ASJ exome AF: 0.730

Gnomad EAS exome AF: 0.857

Gnomad SAS exome AF: 0.737

Gnomad FIN exome AF: 0.752

Gnomad NFE exome AF: 0.737

Gnomad OTH exome AF: 0.746

GnomAD4 exome AF: 0.746 AC: 1073721 AN: 1439430 Hom.: 401297 Cov.: 26 AF XY: 0.745 AC XY: 534642 AN XY: 717604

Gnomad4 AFR exome AF: 0.770

Gnomad4 AMR exome AF: 0.718

Gnomad4 ASJ exome AF: 0.730

Gnomad4 EAS exome AF: 0.861

Gnomad4 SAS exome AF: 0.737

Gnomad4 FIN exome AF: 0.747

Gnomad4 NFE exome AF: 0.743

Gnomad4 OTH exome AF: 0.755

GnomAD4 genome AF: 0.755 AC: 114739 AN: 152068 Hom.: 43295 Cov.: 31 AF XY: 0.754 AC XY: 56022 AN XY: 74332

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.751

Alfa AF: 0.743 Hom.: 24926

Bravo AF: 0.755

Asia WGS AF: 0.781 AC: 2717 AN: 3478

EpiCase AF: 0.735

EpiControl AF: 0.732

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	18
Dann	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0040
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: rs9333288; hg19: chr2-187487160;