rs1448427

Variant names:

• chr2-186661945-G-A
• rs1448427
• NM_002210.5:c.1858-1823G>A

Variant summary

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

The NM_002210.5(ITGAV):​c.1858-1823G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,778 control chromosomes in the GnomAD database, including 8,376 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 0.31 (8376 hom., cov: 32)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 7 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]

ENSG00000227227 (HGNC:41242):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.1858-1823G>A		intron_variant	Intron 18 of 29	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.1750-1823G>A		intron_variant	Intron 16 of 27		NP_001138472.2
ITGAV	NM_001144999.3	c.1720-1823G>A		intron_variant	Intron 18 of 29		NP_001138471.2
ITGAV	XM_047444225.1	c.1015-1823G>A		intron_variant	Intron 14 of 25		XP_047300181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.1858-1823G>A		intron_variant	Intron 18 of 29	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47469 AN: 151660 Hom.: 8357 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.313 AC: 47537 AN: 151778 Hom.: 8376 Cov.: 32 AF XY: 0.321 AC XY: 23840 AN XY: 74176

African (AFR) AF: 0.377 AC: 15611 AN: 41356

American (AMR) AF: 0.377 AC: 5752 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 746 AN: 3464

East Asian (EAS) AF: 0.764 AC: 3935 AN: 5148

South Asian (SAS) AF: 0.198 AC: 953 AN: 4806

European-Finnish (FIN) AF: 0.378 AC: 3975 AN: 10510

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15769 AN: 67936

Other (OTH) AF: 0.309 AC: 650 AN: 2104

Alfa AF: 0.253 Hom.: 8601

Bravo AF: 0.324

Asia WGS AF: 0.456 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.42
DANN	Benign	0.79
PhyloP100		-0.018
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: rs1448427; hg19: chr2-187526672;