rs2227729

Positions:

• chr17-28367275-A-G

Variant summary

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

The ENST00000555059.2(ENSG00000273171):​c.329+176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 818,488 control chromosomes in the GnomAD database, including 4,727 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 0.12 (1289 hom., cov: 32)
  • Exomes 𝑓: 0.092 (3438 hom.)
• Consequence: ENSG00000273171 ENST00000555059.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352

Genes affected

ENSG00000273171 (HGNC:):

VTN (HGNC:12724): (vitronectin) The protein encoded by this gene functions in part as an adhesive glycoprotein. Differential expression of this protein can promote either cell adhesion or migration as it links cells to the extracellular matrix through a variety of ligands. These ligands include integrins, plasminogen activator inhibitor-1, and urokinase plasminogen activator receptor. This secreted protein can be present in the plasma as a monomer or dimer and forms a multimer in the extracellular matrix of several tissues. This protein also inhibits the membrane-damaging effect of the terminal cytolytic complement pathway and binds to several serpin serine protease inhibitors. This protein can also promote extracellular matrix degradation and thus plays a role in tumorigenesis. It is involved in a variety of other biological processes such as the regulation of the coagulation pathway, wound healing, and tissue remodeling. The heparin-binding domain of this protein give it anti-microbial properties. It is also a lipid binding protein that forms a principal component of high density lipoprotein. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Benign. Variant got -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 = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.28367275A>G		intergenic_region
VTN	NM_000638.4	c.*94T>C		downstream_gene_variant		ENST00000226218.9	NP_000629.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000273171	ENST00000555059.2	c.329+176T>C		intron_variant		4		ENSP00000452347.3
SARM1	ENST00000379061.8	n.170+2110A>G		intron_variant		2
ENSG00000258924	ENST00000591482.1	n.555+6428A>G		intron_variant		2
VTN	ENST00000226218.9	c.*94T>C		downstream_gene_variant		1	NM_000638.4	ENSP00000226218.4

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17892 AN: 151984 Hom.: 1275 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0959

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0801

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.0921 AC: 61388 AN: 666386 Hom.: 3438 Cov.: 9 AF XY: 0.0937 AC XY: 32028 AN XY: 341760

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.0813

Gnomad4 ASJ exome AF: 0.0739

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.0770

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.118 AC: 17942 AN: 152102 Hom.: 1289 Cov.: 32 AF XY: 0.120 AC XY: 8918 AN XY: 74348

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.0958

Gnomad4 ASJ AF: 0.0787

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0800

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0855 Hom.: 522

Bravo AF: 0.118

Asia WGS AF: 0.233 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.55

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: rs2227729; hg19: chr17-26694296;