chr2-186638499-T-C

Variant names:

• chr2-186638499-T-C
• rs4667108
• NM_002210.5:c.903+34T>C

Variant summary

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

The NM_002210.5(ITGAV):​c.903+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,552,480 control chromosomes in the GnomAD database, including 129,488 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 0.43 (14539 hom., cov: 32)
  • Exomes 𝑓: 0.40 (114949 hom.)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.903+34T>C		intron_variant	Intron 10 of 29	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.795+34T>C		intron_variant	Intron 8 of 27		NP_001138472.2
ITGAV	NM_001144999.3	c.765+34T>C		intron_variant	Intron 10 of 29		NP_001138471.2
ITGAV	XM_047444225.1	c.60+34T>C		intron_variant	Intron 6 of 25		XP_047300181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.903+34T>C		intron_variant	Intron 10 of 29	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65501 AN: 151838 Hom.: 14518 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.434

GnomAD2 exomes AF: 0.438 AC: 108659 AN: 247880 AF XY: 0.427

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.508

Gnomad ASJ exome AF: 0.436

Gnomad EAS exome AF: 0.781

Gnomad FIN exome AF: 0.484

Gnomad NFE exome AF: 0.377

Gnomad OTH exome AF: 0.423

GnomAD4 exome AF: 0.397 AC: 555476 AN: 1400524 Hom.: 114949 Cov.: 23 AF XY: 0.394 AC XY: 275756 AN XY: 700244

African (AFR) AF: 0.475 AC: 15224 AN: 32050

American (AMR) AF: 0.504 AC: 22288 AN: 44258

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 11090 AN: 25756

East Asian (EAS) AF: 0.788 AC: 31025 AN: 39388

South Asian (SAS) AF: 0.334 AC: 28230 AN: 84464

European-Finnish (FIN) AF: 0.471 AC: 25120 AN: 53314

Middle Eastern (MID) AF: 0.396 AC: 1594 AN: 4028

European-Non Finnish (NFE) AF: 0.375 AC: 397268 AN: 1059098

Other (OTH) AF: 0.406 AC: 23637 AN: 58168

GnomAD4 genome AF: 0.432 AC: 65572 AN: 151956 Hom.: 14539 Cov.: 32 AF XY: 0.438 AC XY: 32531 AN XY: 74256

African (AFR) AF: 0.468 AC: 19410 AN: 41440

American (AMR) AF: 0.462 AC: 7045 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1452 AN: 3470

East Asian (EAS) AF: 0.766 AC: 3970 AN: 5180

South Asian (SAS) AF: 0.332 AC: 1593 AN: 4804

European-Finnish (FIN) AF: 0.493 AC: 5194 AN: 10546

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25510 AN: 67934

Other (OTH) AF: 0.434 AC: 918 AN: 2114

Alfa AF: 0.394 Hom.: 16743

Bravo AF: 0.437

Asia WGS AF: 0.513 AC: 1783 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.41
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs4667108; hg19: chr2-187503226;