17-28367462-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4BP6BP7BA1

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 was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.234).

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

GnomAD2 exomes

AF:

0.110

AC:

27448

AN:

250188

AF XY:

0.111

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 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

African (AFR)

AF:

0.157

AC:

5239

AN:

33430

American (AMR)

AF:

0.0867

AC:

3863

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.0749

AC:

1957

AN:

26112

East Asian (EAS)

AF:

0.191

AC:

7568

AN:

39690

South Asian (SAS)

AF:

0.159

AC:

13708

AN:

86168

European-Finnish (FIN)

AF:

0.107

AC:

5686

AN:

53362

Middle Eastern (MID)

AF:

0.0887

AC:

511

AN:

5760

European-Non Finnish (NFE)

AF:

0.0781

AC:

86827

AN:

1111588

Other (OTH)

AF:

0.103

AC:

6203

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

5508

11015

16523

22030

27538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.111

AC:

16923

AN:

152162

Hom.:

1111

Cov.:

AF XY:

0.113

AC XY:

8419

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.150

AC:

6238

AN:

41502

American (AMR)

AF:

0.0937

AC:

1433

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0786

AC:

273

AN:

3472

East Asian (EAS)

AF:

0.232

AC:

1196

AN:

5158

South Asian (SAS)

AF:

0.180

AC:

869

AN:

4818

European-Finnish (FIN)

AF:

0.108

AC:

1140

AN:

10592

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0800

AC:

5439

AN:

68010

Other (OTH)

AF:

0.116

AC:

245

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

754

1509

2263

3018

3772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0934

Hom.:

1324

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

(source)

DANN

Benign

0.79

PhyloP100

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

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17-28367462-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over