5-83539726-A-G

Position:

chr5-83539726-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004385.5(VCAN):c.6723A>G(p.Arg2241Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,613,372 control chromosomes in the GnomAD database, including 190,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19064 hom., cov: 32)

Exomes 𝑓: 0.48 ( 171739 hom. )

Consequence

VCAN
NM_004385.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.423

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 5-83539726-A-G is Benign according to our data. Variant chr5-83539726-A-G is described in ClinVar as [Benign]. Clinvar id is 198797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-83539726-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.423 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.516 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.6723A>G	p.Arg2241Arg	synonymous_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.6723A>G	p.Arg2241Arg	synonymous_variant	8/15	1	NM_004385.5	ENSP00000265077.3		P13611-1

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75894

AN:

151866

Hom.:

19051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.504

Gnomad AMI

AF:

0.683

Gnomad AMR

AF:

0.526

Gnomad ASJ

AF:

0.582

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.493

Gnomad OTH

AF:

0.535

GnomAD3 exomes

AF:

0.485

AC:

121044

AN:

249592

Hom.:

29626

AF XY:

0.479

AC XY:

64635

AN XY:

134964

show subpopulations

Gnomad AFR exome

AF:

0.504

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.399

Gnomad SAS exome

AF:

0.387

Gnomad FIN exome

AF:

0.513

Gnomad NFE exome

AF:

0.498

Gnomad OTH exome

AF:

0.495

GnomAD4 exome

AF:

0.484

AC:

707047

AN:

1461386

Hom.:

171739

Cov.:

AF XY:

0.481

AC XY:

349651

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.499

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.575

Gnomad4 EAS exome

AF:

0.463

Gnomad4 SAS exome

AF:

0.389

Gnomad4 FIN exome

AF:

0.508

Gnomad4 NFE exome

AF:

0.487

Gnomad4 OTH exome

AF:

0.480

GnomAD4 genome

AF:

0.500

AC:

75941

AN:

151986

Hom.:

19064

Cov.:

AF XY:

0.499

AC XY:

37045

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.504

Gnomad4 AMR

AF:

0.526

Gnomad4 ASJ

AF:

0.582

Gnomad4 EAS

AF:

0.409

Gnomad4 SAS

AF:

0.392

Gnomad4 FIN

AF:

0.529

Gnomad4 NFE

AF:

0.493

Gnomad4 OTH

AF:

0.536

Alfa

AF:

0.498

Hom.:

13300

Bravo

AF:

0.499

Asia WGS

AF:

0.411

AC:

1426

AN:

3478

EpiCase

AF:

0.502

EpiControl

AF:

0.503

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	Eurofins Ntd Llc (ga)	Jun 12, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 01, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Vitreoretinopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

DANN

Benign

0.62

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