rs2227720

chr17-28370500-A-Gchr17-28370500-A-T

Variant summary

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

The ENST00000542029.1(VTN):c.-67-230T>C variant causes a intron 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 ENST00000542029.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VTN	ENST00000542029.1	c.-67-230T>C		intron_variant		3
SARM1	ENST00000379061.8	n.170+5335A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.0942

Gnomad4 ASJ exome AF: 0.0784

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.0802

Gnomad4 OTH exome AF: 0.0983

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

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0809

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0813

Gnomad4 OTH AF: 0.118

Alfa AF: 0.101 Hom.: 159

Bravo AF: 0.120

Asia WGS AF: 0.225 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.6
Dann	Benign	0.46

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: rs2227720; hg19: chr17-26697521;