chr5-83512253-C-T

Position:

chr5-83512253-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004385.5(VCAN):c.899C>T(p.Ser300Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,614,130 control chromosomes in the GnomAD database, including 1,350 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 141 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1209 hom. )

Consequence

VCAN
NM_004385.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

VCAN (HGNC:2464): (versican) This gene is a member of the aggrecan/versican proteoglycan family. The protein encoded is a large chondroitin sulfate proteoglycan and is a major component of the extracellular matrix. This protein is involved in cell adhesion, proliferation, proliferation, migration and angiogenesis and plays a central role in tissue morphogenesis and maintenance. Mutations in this gene are the cause of Wagner syndrome type 1. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

VCAN links:

VCAN (HGNC:):

VCAN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040576756).

BP6

Variant 5-83512253-C-T is Benign according to our data. Variant chr5-83512253-C-T is described in ClinVar as [Benign]. Clinvar id is 198170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-83512253-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCAN	NM_004385.5 linkuse as main transcript	c.899C>T	p.Ser300Leu	missense_variant	6/15	ENST00000265077.8	NP_004376.2	P13611-1A0A024RAQ9Q59FG9
VCAN	NM_001164097.2 linkuse as main transcript	c.899C>T	p.Ser300Leu	missense_variant	6/14		NP_001157569.1	P13611-2A0A024RAL1Q6MZK8
VCAN	NM_001164098.2 linkuse as main transcript	c.899C>T	p.Ser300Leu	missense_variant	6/14		NP_001157570.1	P13611-3A0A024RAP3
VCAN	NM_001126336.3 linkuse as main transcript	c.899C>T	p.Ser300Leu	missense_variant	6/13		NP_001119808.1	P13611-4Q86W61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8 linkuse as main transcript	c.899C>T	p.Ser300Leu	missense_variant	6/15	1	NM_004385.5	ENSP00000265077.3		P13611-1

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2275

AN:

152146

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00454

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00583

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00611

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.0315

AC:

7927

AN:

251294

Hom.:

642

AF XY:

0.0346

AC XY:

4704

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00314

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00338

Gnomad EAS exome

AF:

0.212

Gnomad SAS exome

AF:

0.0970

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.00622

Gnomad OTH exome

AF:

0.0170

GnomAD4 exome

AF:

0.0151

AC:

22099

AN:

1461866

Hom.:

1209

Cov.:

AF XY:

0.0176

AC XY:

12794

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00460

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.00367

Gnomad4 EAS exome

AF:

0.163

Gnomad4 SAS exome

AF:

0.0935

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.00498

Gnomad4 OTH exome

AF:

0.0233

GnomAD4 genome

AF:

0.0149

AC:

2267

AN:

152264

Hom.:

141

Cov.:

AF XY:

0.0168

AC XY:

1249

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00455

Gnomad4 AMR

AF:

0.00582

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00612

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0109

Hom.:

129

Bravo

AF:

0.0137

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.00605

AC:

ExAC

AF:

0.0323

AC:

3921

Asia WGS

AF:

0.128

AC:

443

AN:

3478

EpiCase

AF:

0.00725

EpiControl

AF:

0.00634

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 10, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Wagner syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Vitreoretinopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.12

T;.;.;T;.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.83

T;T;T;T;T;T;T

MetaRNN

Benign

0.0041

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L;L;.;.;.;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.8

N;D;D;D;D;D;N

REVEL

Benign

0.092

Sift

Benign

0.30

T;T;T;T;T;D;D

Sift4G

Benign

0.18

T;T;T;T;T;T;T

Polyphen

0.010

B;B;B;.;.;B;B

Vest4

0.38

MPC

0.079

ClinPred

0.0031

GERP RS

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.86

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

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