ENST00000886528.1:c.-297T>C

Variant names:

• chr17-28370500-A-G
• rs2227720
• ENST00000886528.1:c.-297T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000886528.1(VTN):​c.-297T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 370,456 control chromosomes in the GnomAD database, including 2,670 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 (1310 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1360 hom.)
• Consequence: VTN ENST00000886528.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 6 publications found

Genes affected

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]

SARM1 (HGNC:17074): (sterile alpha and TIR motif containing 1) Enables NAD+ nucleotidase, cyclic ADP-ribose generating and identical protein binding activity. Involved in NAD catabolic process; positive regulation of neuron death; and response to axon injury. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258924 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000886528.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTN	NM_000638.4	MANE Select	c.-297T>C		upstream_gene	N/A	NP_000629.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTN	ENST00000886528.1		c.-297T>C		5_prime_UTR	Exon 1 of 7	ENSP00000556587.1
	VTN	ENST00000886529.1		c.-67-230T>C		intron	N/A	ENSP00000556588.1
	VTN	ENST00000886530.1		c.-67-230T>C		intron	N/A	ENSP00000556589.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18242 AN: 152086 Hom.: 1296 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.101 AC: 22041 AN: 218252 Hom.: 1360 Cov.: 0 AF XY: 0.102 AC XY: 11531 AN XY: 112894

African (AFR) AF: 0.184 AC: 1424 AN: 7740

American (AMR) AF: 0.0942 AC: 791 AN: 8396

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 558 AN: 7118

East Asian (EAS) AF: 0.185 AC: 2721 AN: 14686

South Asian (SAS) AF: 0.150 AC: 2764 AN: 18480

European-Finnish (FIN) AF: 0.121 AC: 1631 AN: 13462

Middle Eastern (MID) AF: 0.0925 AC: 98 AN: 1060

European-Non Finnish (NFE) AF: 0.0802 AC: 10754 AN: 134080

Other (OTH) AF: 0.0983 AC: 1300 AN: 13230

GnomAD4 genome AF: 0.120 AC: 18290 AN: 152204 Hom.: 1310 Cov.: 32 AF XY: 0.123 AC XY: 9135 AN XY: 74414

African (AFR) AF: 0.174 AC: 7211 AN: 41536

American (AMR) AF: 0.104 AC: 1592 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 281 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1186 AN: 5172

South Asian (SAS) AF: 0.180 AC: 868 AN: 4820

European-Finnish (FIN) AF: 0.122 AC: 1286 AN: 10582

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0813 AC: 5527 AN: 68010

Other (OTH) AF: 0.118 AC: 249 AN: 2110

Alfa AF: 0.103 Hom.: 166

Bravo AF: 0.120

Asia WGS AF: 0.225 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.46
PhyloP100		-0.21
PromoterAI		-0.024	Neutral
Mutation Taster		=300/0	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: rs2227720; hg19: chr17-26697521;