rs2227721

Variant names:

• chr17-28370430-C-A
• rs2227721
• ENST00000542029.1:c.-67-160G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-28370430-C-A
• chr17-28370430-C-G
• chr17-28370430-C-T

Variant summary

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

The ENST00000542029.1(VTN):​c.-67-160G>T variant causes a intron 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 ENST00000542029.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.920

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTN	NM_000638.4	c.-227G>T		upstream_gene_variant		ENST00000226218.9	NP_000629.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTN	ENST00000542029.1	c.-67-160G>T		intron_variant	Intron 1 of 3	3		ENSP00000440439.1
SARM1	ENST00000379061.8	n.170+5265C>A		intron_variant	Intron 2 of 10	2
ENSG00000258924	ENST00000591482.1	n.555+9583C>A		intron_variant	Intron 5 of 5	2
VTN	ENST00000226218.9	c.-227G>T		upstream_gene_variant		1	NM_000638.4	ENSP00000226218.4

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

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.0961

Gnomad4 ASJ exome AF: 0.0783

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.0807

Gnomad4 OTH exome AF: 0.105

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

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0810

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0814

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0592 Hom.: 80

Bravo AF: 0.120

Asia WGS AF: 0.230 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs2227721; hg19: chr17-26697451;