rs1839123

Positions:

• chr2-186678647-C-T

Variant summary

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

The NM_002210.5(ITGAV):​c.*1355C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 441,634 control chromosomes in the GnomAD database, including 20,154 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 0.27 (5699 hom., cov: 32)
  • Exomes 𝑓: 0.31 (14455 hom.)
• Consequence: ITGAV NM_002210.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.*1355C>T		3_prime_UTR_variant	30/30	ENST00000261023.8	NP_002201.2
ITGAV	NM_001144999.3	c.*1355C>T		3_prime_UTR_variant	30/30		NP_001138471.2
ITGAV	NM_001145000.3	c.*1355C>T		3_prime_UTR_variant	28/28		NP_001138472.2
ITGAV	XM_047444225.1	c.*1355C>T		3_prime_UTR_variant	26/26		XP_047300181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.*1355C>T		3_prime_UTR_variant	30/30	1	NM_002210.5	ENSP00000261023	P2
	ENST00000453665.1	n.131+16510G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41104 AN: 151750 Hom.: 5698 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.309 AC: 89576 AN: 289766 Hom.: 14455 Cov.: 0 AF XY: 0.317 AC XY: 52384 AN XY: 165388

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.378

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.298

GnomAD4 genome AF: 0.271 AC: 41123 AN: 151868 Hom.: 5699 Cov.: 32 AF XY: 0.270 AC XY: 20037 AN XY: 74216

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.283

Alfa AF: 0.293 Hom.: 1451

Bravo AF: 0.268

Asia WGS AF: 0.265 AC: 924 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.1
DANN	Benign	0.67

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: rs1839123; hg19: chr2-187543374;