chr17-28367462-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000638.4(VTN):c.1344T>C(p.Asn448Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,613,202 control chromosomes in the GnomAD database, including 8,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 1111 hom., cov: 32)

Exomes 𝑓: 0.090 ( 6901 hom. )

Consequence

VTN
NM_000638.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.99

Variant links:

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]

VTN links:

ENSG00000273171 (HGNC:):

ENSG00000273171 links:

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]

SARM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 17-28367462-A-G is Benign according to our data. Variant chr17-28367462-A-G is described in ClinVar as [Benign]. Clinvar id is 3059030.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-28367462-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.99 with no splicing effect.

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 link	c.1344T>C	p.Asn448Asn	synonymous_variant	Exon 8 of 8	ENST00000226218.9	NP_000629.3	P04004D9ZGG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VTN	ENST00000226218.9 link	c.1344T>C	p.Asn448Asn	synonymous_variant	Exon 8 of 8	1	NM_000638.4	ENSP00000226218.4	P04004
ENSG00000273171	ENST00000555059.2 link	c.318T>C	p.Asn106Asn	synonymous_variant	Exon 2 of 4	4		ENSP00000452347.3	H0YJW9
SARM1	ENST00000379061.8 link	n.170+2297A>G		intron_variant	Intron 2 of 10	2
ENSG00000258924	ENST00000591482.1 link	n.555+6615A>G		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16874

AN:

152044

Hom.:

1098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.0714

Gnomad AMR

AF:

0.0938

Gnomad ASJ

AF:

0.0786

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0800

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.110

AC:

27448

AN:

250188

Hom.:

1814

AF XY:

0.111

AC XY:

15021

AN XY:

135434

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.0898

Gnomad ASJ exome

AF:

0.0756

Gnomad EAS exome

AF:

0.233

Gnomad SAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0807

Gnomad OTH exome

AF:

0.0916

GnomAD4 exome

AF:

0.0900

AC:

131562

AN:

1461040

Hom.:

6901

Cov.:

AF XY:

0.0922

AC XY:

66979

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.0867

Gnomad4 ASJ exome

AF:

0.0749

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.0781

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.111

AC:

16923

AN:

152162

Hom.:

1111

Cov.:

AF XY:

0.113

AC XY:

8419

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.0937

Gnomad4 ASJ

AF:

0.0786

Gnomad4 EAS

AF:

0.232

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.0800

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.0871

Hom.:

778

Bravo

AF:

0.110

Asia WGS

AF:

0.233

AC:

808

AN:

3478

EpiCase

AF:

0.0798

EpiControl

AF:

0.0776

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

VTN-related disorder

Benign:1

Nov 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.6

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over