rs2548541

Positions:

chr5-83537326-G-A

Variant summary

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

The NM_004385.5(VCAN):c.4323G>A(p.Gln1441=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 1,613,732 control chromosomes in the GnomAD database, including 315,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35430 hom., cov: 32)

Exomes 𝑓: 0.62 ( 280193 hom. )

Consequence

VCAN
NM_004385.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.634

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-AS1 (HGNC:40163): (VCAN antisense RNA 1)

VCAN-AS1 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=-0.68).

BP6

Variant 5-83537326-G-A is Benign according to our data. Variant chr5-83537326-G-A is described in ClinVar as [Benign]. Clinvar id is 198803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-83537326-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.634 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 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.4323G>A	p.Gln1441=	synonymous_variant	8/15	ENST00000265077.8	NP_004376.2
VCAN-AS1	NR_136215.1 linkuse as main transcript	n.285-3153C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8 linkuse as main transcript	c.4323G>A	p.Gln1441=	synonymous_variant	8/15	1	NM_004385.5	ENSP00000265077		P13611-1

Frequencies

GnomAD3 genomes

AF:

0.677

AC:

102774

AN:

151908

Hom.:

35382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.805

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.712

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.720

Gnomad FIN

AF:

0.669

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.609

Gnomad OTH

AF:

0.698

GnomAD3 exomes

AF:

0.643

AC:

161062

AN:

250626

Hom.:

52259

AF XY:

0.644

AC XY:

87236

AN XY:

135410

show subpopulations

Gnomad AFR exome

AF:

0.808

Gnomad AMR exome

AF:

0.589

Gnomad ASJ exome

AF:

0.715

Gnomad EAS exome

AF:

0.629

Gnomad SAS exome

AF:

0.704

Gnomad FIN exome

AF:

0.654

Gnomad NFE exome

AF:

0.613

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.617

AC:

902380

AN:

1461702

Hom.:

280193

Cov.:

AF XY:

0.620

AC XY:

450726

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.813

Gnomad4 AMR exome

AF:

0.594

Gnomad4 ASJ exome

AF:

0.711

Gnomad4 EAS exome

AF:

0.658

Gnomad4 SAS exome

AF:

0.702

Gnomad4 FIN exome

AF:

0.648

Gnomad4 NFE exome

AF:

0.599

Gnomad4 OTH exome

AF:

0.635

GnomAD4 genome

AF:

0.677

AC:

102877

AN:

152030

Hom.:

35430

Cov.:

AF XY:

0.681

AC XY:

50569

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.805

Gnomad4 AMR

AF:

0.623

Gnomad4 ASJ

AF:

0.712

Gnomad4 EAS

AF:

0.635

Gnomad4 SAS

AF:

0.719

Gnomad4 FIN

AF:

0.669

Gnomad4 NFE

AF:

0.609

Gnomad4 OTH

AF:

0.698

Alfa

AF:

0.633

Hom.:

41405

Bravo

AF:

0.674

Asia WGS

AF:

0.663

AC:

2303

AN:

3478

EpiCase

AF:

0.622

EpiControl

AF:

0.623

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

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)	Jun 08, 2014	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
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 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

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.14

DANN

Benign

0.81

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