rs3816386

Variant names:

• chr2-186663908-A-G
• rs3816386
• NM_002210.5:c.1925+73A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.83).
• 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 rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.1925+73A>G		intron_variant	Intron 19 of 29	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.1817+73A>G		intron_variant	Intron 17 of 27		NP_001138472.2
ITGAV	NM_001144999.3	c.1787+73A>G		intron_variant	Intron 19 of 29		NP_001138471.2
ITGAV	XM_047444225.1	c.1082+73A>G		intron_variant	Intron 15 of 25		XP_047300181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.1925+73A>G		intron_variant	Intron 19 of 29	1	NM_002210.5	ENSP00000261023.3

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

African (AFR) AF: 0.214 AC: 4390 AN: 20470

American (AMR) AF: 0.311 AC: 12204 AN: 39232

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 7238 AN: 21488

East Asian (EAS) AF: 0.116 AC: 4169 AN: 35882

South Asian (SAS) AF: 0.388 AC: 26817 AN: 69122

European-Finnish (FIN) AF: 0.270 AC: 13026 AN: 48276

Middle Eastern (MID) AF: 0.366 AC: 1552 AN: 4242

European-Non Finnish (NFE) AF: 0.299 AC: 161147 AN: 538592

Other (OTH) AF: 0.293 AC: 11403 AN: 38964

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

African (AFR) AF: 0.211 AC: 8770 AN: 41504

American (AMR) AF: 0.287 AC: 4375 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3468

East Asian (EAS) AF: 0.145 AC: 754 AN: 5184

South Asian (SAS) AF: 0.381 AC: 1834 AN: 4814

European-Finnish (FIN) AF: 0.257 AC: 2718 AN: 10584

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20578 AN: 67950

Other (OTH) AF: 0.288 AC: 608 AN: 2112

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
PhyloP100		1.4
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: rs3816386; hg19: chr2-187528635; COSMIC: COSV53710465; COSMIC: COSV53710465;