ENST00000886528.1:c.-227G>T

Variant names:

• chr17-28370430-C-A
• rs2227721
• ENST00000886528.1:c.-227G>T

Variant summary

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

The ENST00000886528.1(VTN):​c.-227G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 556,178 control chromosomes in the GnomAD database, including 3,875 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 (1315 hom., cov: 32)
  • Exomes 𝑓: 0.10 (2560 hom.)
• Consequence: VTN ENST00000886528.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.920
• Publications: 13 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTN	NM_000638.4	MANE Select	c.-227G>T		upstream_gene	N/A	NP_000629.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTN	ENST00000886528.1		c.-227G>T		5_prime_UTR	Exon 1 of 7	ENSP00000556587.1
	VTN	ENST00000886529.1		c.-67-160G>T		intron	N/A	ENSP00000556588.1
	VTN	ENST00000886530.1		c.-67-160G>T		intron	N/A	ENSP00000556589.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18252 AN: 152058 Hom.: 1301 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0810

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0814

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.103 AC: 41436 AN: 404002 Hom.: 2560 Cov.: 4 AF XY: 0.105 AC XY: 22048 AN XY: 210874

African (AFR) AF: 0.183 AC: 2139 AN: 11714

American (AMR) AF: 0.0961 AC: 1513 AN: 15744

Ashkenazi Jewish (ASJ) AF: 0.0783 AC: 977 AN: 12478

East Asian (EAS) AF: 0.182 AC: 5092 AN: 27972

South Asian (SAS) AF: 0.156 AC: 6035 AN: 38590

European-Finnish (FIN) AF: 0.122 AC: 3219 AN: 26436

Middle Eastern (MID) AF: 0.0867 AC: 154 AN: 1776

European-Non Finnish (NFE) AF: 0.0807 AC: 19842 AN: 245806

Other (OTH) AF: 0.105 AC: 2465 AN: 23486

GnomAD4 genome AF: 0.120 AC: 18300 AN: 152176 Hom.: 1315 Cov.: 32 AF XY: 0.123 AC XY: 9145 AN XY: 74412

African (AFR) AF: 0.173 AC: 7201 AN: 41506

American (AMR) AF: 0.104 AC: 1593 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0810 AC: 281 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1198 AN: 5174

South Asian (SAS) AF: 0.180 AC: 867 AN: 4820

European-Finnish (FIN) AF: 0.121 AC: 1285 AN: 10584

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0814 AC: 5535 AN: 68008

Other (OTH) AF: 0.119 AC: 251 AN: 2112

Alfa AF: 0.0628 Hom.: 88

Bravo AF: 0.120

Asia WGS AF: 0.230 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.62
PhyloP100		0.92
PromoterAI		-0.091	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2227721; hg19: chr17-26697451;