chr2-186590551-C-T

Position:

• chr2-186590551-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000261023.8(ITGAV):​c.185+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 1,596,300 control chromosomes in the GnomAD database, including 439,041 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 0.70 (37861 hom., cov: 33)
  • Exomes 𝑓: 0.74 (401180 hom.)
• Consequence: ITGAV ENST00000261023.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.185+28C>T		intron_variant		ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.185+28C>T		intron_variant			NP_001138472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.185+28C>T		intron_variant		1	NM_002210.5	ENSP00000261023	P2

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106710 AN: 151980 Hom.: 37835 Cov.: 33

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.719

GnomAD3 exomes AF: 0.737 AC: 168154 AN: 228064 Hom.: 62132 AF XY: 0.741 AC XY: 92311 AN XY: 124628

Gnomad AFR exome AF: 0.584

Gnomad AMR exome AF: 0.709

Gnomad ASJ exome AF: 0.731

Gnomad EAS exome AF: 0.860

Gnomad SAS exome AF: 0.738

Gnomad FIN exome AF: 0.755

Gnomad NFE exome AF: 0.744

Gnomad OTH exome AF: 0.747

GnomAD4 exome AF: 0.745 AC: 1075352 AN: 1444204 Hom.: 401180 Cov.: 31 AF XY: 0.744 AC XY: 534495 AN XY: 717956

Gnomad4 AFR exome AF: 0.578

Gnomad4 AMR exome AF: 0.714

Gnomad4 ASJ exome AF: 0.730

Gnomad4 EAS exome AF: 0.862

Gnomad4 SAS exome AF: 0.737

Gnomad4 FIN exome AF: 0.749

Gnomad4 NFE exome AF: 0.747

Gnomad4 OTH exome AF: 0.748

GnomAD4 genome AF: 0.702 AC: 106782 AN: 152096 Hom.: 37861 Cov.: 33 AF XY: 0.702 AC XY: 52218 AN XY: 74342

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.716

Alfa AF: 0.716 Hom.: 7276

Bravo AF: 0.695

Asia WGS AF: 0.768 AC: 2669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.3
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9333287; hg19: chr2-187455278;