NM_002210.5:c.1719+132C>A

Variant names:

• chr2-186656533-C-A
• rs3738919
• NM_002210.5:c.1719+132C>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.1719+132C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 648,170 control chromosomes in the GnomAD database, including 34,871 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 (6820 hom., cov: 32)
  • Exomes 𝑓: 0.33 (28051 hom.)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 25 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 (NFE) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.1719+132C>A		intron_variant	Intron 17 of 29	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.1611+132C>A		intron_variant	Intron 15 of 27		NP_001138472.2
ITGAV	NM_001144999.3	c.1581+132C>A		intron_variant	Intron 17 of 29		NP_001138471.2
ITGAV	XM_047444225.1	c.876+132C>A		intron_variant	Intron 13 of 25		XP_047300181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.1719+132C>A		intron_variant	Intron 17 of 29	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43159 AN: 151930 Hom.: 6821 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.326 AC: 161975 AN: 496122 Hom.: 28051 AF XY: 0.329 AC XY: 84212 AN XY: 256146

African (AFR) AF: 0.174 AC: 1860 AN: 10688

American (AMR) AF: 0.225 AC: 2339 AN: 10392

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 4527 AN: 12932

East Asian (EAS) AF: 0.0880 AC: 2255 AN: 25618

South Asian (SAS) AF: 0.326 AC: 10286 AN: 31532

European-Finnish (FIN) AF: 0.299 AC: 11649 AN: 38942

Middle Eastern (MID) AF: 0.421 AC: 1166 AN: 2772

European-Non Finnish (NFE) AF: 0.354 AC: 119082 AN: 336266

Other (OTH) AF: 0.327 AC: 8811 AN: 26980

GnomAD4 genome AF: 0.284 AC: 43157 AN: 152048 Hom.: 6820 Cov.: 32 AF XY: 0.280 AC XY: 20839 AN XY: 74314

African (AFR) AF: 0.174 AC: 7211 AN: 41488

American (AMR) AF: 0.257 AC: 3923 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1226 AN: 3468

East Asian (EAS) AF: 0.0786 AC: 406 AN: 5168

South Asian (SAS) AF: 0.326 AC: 1569 AN: 4812

European-Finnish (FIN) AF: 0.305 AC: 3212 AN: 10540

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24423 AN: 67978

Other (OTH) AF: 0.298 AC: 628 AN: 2110

Alfa AF: 0.330 Hom.: 27717

Bravo AF: 0.274

Asia WGS AF: 0.217 AC: 757 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	1.6
DANN	Benign	0.55
PhyloP100		-0.084
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: rs3738919; hg19: chr2-187521260;