rs3816386

Positions:

• chr2-186663908-A-G

Variant summary

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

The NM_002210.5(ITGAV):​c.1925+73A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 968,354 control chromosomes in the GnomAD database, including 42,975 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 (5732 hom., cov: 32)
  • Exomes 𝑓: 0.30 (37243 hom.)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.1925+73A>G		intron_variant		ENST00000261023.8	NP_002201.2
ITGAV	NM_001144999.3	c.1787+73A>G		intron_variant			NP_001138471.2
ITGAV	NM_001145000.3	c.1817+73A>G		intron_variant			NP_001138472.2
ITGAV	XM_047444225.1	c.1082+73A>G		intron_variant			XP_047300181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.1925+73A>G		intron_variant		1	NM_002210.5	ENSP00000261023	P2
	ENST00000453665.1	n.132-3327T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41213 AN: 151968 Hom.: 5731 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.296 AC: 241946 AN: 816268 Hom.: 37243 AF XY: 0.301 AC XY: 129301 AN XY: 428964

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.271 AC: 41239 AN: 152086 Hom.: 5732 Cov.: 32 AF XY: 0.271 AC XY: 20124 AN XY: 74352

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.288

Alfa AF: 0.292 Hom.: 1297

Bravo AF: 0.268

Asia WGS AF: 0.268 AC: 932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.61

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: rs3816386; hg19: chr2-187528635; COSMIC: COSV53710465; COSMIC: COSV53710465;