chr5-83538480-G-A

Position:

chr5-83538480-G-A

Variant summary

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

The NM_004385.5(VCAN):c.5477G>A(p.Arg1826His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,613,642 control chromosomes in the GnomAD database, including 117,577 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11307 hom., cov: 32)

Exomes 𝑓: 0.38 ( 106270 hom. )

Consequence

VCAN
NM_004385.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.74

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=2.5302172E-4).

BP6

Variant 5-83538480-G-A is Benign according to our data. Variant chr5-83538480-G-A is described in ClinVar as [Benign]. Clinvar id is 167823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-83538480-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.429 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.5477G>A	p.Arg1826His	missense_variant	8/15	ENST00000265077.8	NP_004376.2	P13611-1A0A024RAQ9Q59FG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8 linkuse as main transcript	c.5477G>A	p.Arg1826His	missense_variant	8/15	1	NM_004385.5	ENSP00000265077.3		P13611-1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

58020

AN:

151798

Hom.:

11303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.502

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.417

GnomAD3 exomes

AF:

0.384

AC:

96019

AN:

250096

Hom.:

18761

AF XY:

0.378

AC XY:

51128

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.349

Gnomad AMR exome

AF:

0.457

Gnomad ASJ exome

AF:

0.482

Gnomad EAS exome

AF:

0.344

Gnomad SAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.390

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.396

GnomAD4 exome

AF:

0.379

AC:

554355

AN:

1461726

Hom.:

106270

Cov.:

AF XY:

0.376

AC XY:

273669

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.344

Gnomad4 AMR exome

AF:

0.454

Gnomad4 ASJ exome

AF:

0.480

Gnomad4 EAS exome

AF:

0.410

Gnomad4 SAS exome

AF:

0.275

Gnomad4 FIN exome

AF:

0.388

Gnomad4 NFE exome

AF:

0.382

Gnomad4 OTH exome

AF:

0.373

GnomAD4 genome

AF:

0.382

AC:

58041

AN:

151916

Hom.:

11307

Cov.:

AF XY:

0.380

AC XY:

28220

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.437

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.352

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.402

Gnomad4 NFE

AF:

0.387

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.384

Hom.:

25950

Bravo

AF:

0.385

TwinsUK

AF:

0.389

AC:

1441

ALSPAC

AF:

0.378

AC:

1457

ESP6500AA

AF:

0.352

AC:

1549

ESP6500EA

AF:

0.400

AC:

3441

ExAC

AF:

0.380

AC:

46087

Asia WGS

AF:

0.284

AC:

986

AN:

3476

EpiCase

AF:

0.400

EpiControl

AF:

0.399

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Wagner syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 20, 2014	- -

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	Mar 14, 2020	This variant is associated with the following publications: (PMID: 19655167) -

Vitreoretinopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.089

T;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.37

T;T;T

MetaRNN

Benign

0.00025

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

0.18

N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0020

D;D;D

Sift4G

Benign

0.55

T;T;T

Polyphen

0.23

B;B;.

Vest4

0.034

MPC

0.098

ClinPred

0.020

GERP RS

0.25

Varity_R

0.059

gMVP

0.19

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