5-83490420-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004385.5(VCAN):c.393C>T(p.Asp131Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,614,104 control chromosomes in the GnomAD database, including 542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 73 hom., cov: 32)

Exomes 𝑓: 0.011 ( 469 hom. )

Consequence

VCAN
NM_004385.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.39

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

Wagner disease
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

VCAN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 5-83490420-C-T is Benign according to our data. Variant chr5-83490420-C-T is described in ClinVar as Benign. ClinVar VariationId is 259364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5 link	c.393C>T	p.Asp131Asp	synonymous_variant	Exon 3 of 15	ENST00000265077.8	NP_004376.2	P13611-1A0A024RAQ9Q59FG9
VCAN	NM_001164097.2 link	c.393C>T	p.Asp131Asp	synonymous_variant	Exon 3 of 14		NP_001157569.1	P13611-2A0A024RAL1Q6MZK8
VCAN	NM_001164098.2 link	c.393C>T	p.Asp131Asp	synonymous_variant	Exon 3 of 14		NP_001157570.1	P13611-3A0A024RAP3
VCAN	NM_001126336.3 link	c.393C>T	p.Asp131Asp	synonymous_variant	Exon 3 of 13		NP_001119808.1	P13611-4Q86W61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8 link	c.393C>T	p.Asp131Asp	synonymous_variant	Exon 3 of 15	1	NM_004385.5	ENSP00000265077.3		P13611-1

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

3003

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0209

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0649

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.0697

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.0292

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00498

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0289

AC:

7246

AN:

251108

AF XY:

0.0247

show subpopulations

Gnomad AFR exome

AF:

0.0210

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.00676

Gnomad EAS exome

AF:

0.0737

Gnomad FIN exome

AF:

0.0334

Gnomad NFE exome

AF:

0.00687

Gnomad OTH exome

AF:

0.0209

GnomAD4 exome

AF:

0.0114

AC:

16608

AN:

1461878

Hom.:

469

Cov.:

AF XY:

0.0108

AC XY:

7857

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0205

AC:

687

AN:

33480

American (AMR)

AF:

0.100

AC:

4491

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00888

AC:

232

AN:

26136

East Asian (EAS)

AF:

0.0719

AC:

2856

AN:

39698

South Asian (SAS)

AF:

0.00415

AC:

358

AN:

86258

European-Finnish (FIN)

AF:

0.0311

AC:

1661

AN:

53416

Middle Eastern (MID)

AF:

0.0180

AC:

104

AN:

5768

European-Non Finnish (NFE)

AF:

0.00475

AC:

5279

AN:

1112004

Other (OTH)

AF:

0.0156

AC:

940

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

944

1887

2831

3774

4718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

306

612

918

1224

1530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0198

AC:

3008

AN:

152226

Hom.:

Cov.:

AF XY:

0.0217

AC XY:

1618

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0209

AC:

869

AN:

41528

American (AMR)

AF:

0.0649

AC:

992

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0132

AC:

AN:

3472

East Asian (EAS)

AF:

0.0699

AC:

362

AN:

5178

South Asian (SAS)

AF:

0.00518

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0292

AC:

309

AN:

10592

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00498

AC:

339

AN:

68028

Other (OTH)

AF:

0.0223

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

156

311

467

622

778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.0242

Asia WGS

AF:

0.0440

AC:

151

AN:

3478

EpiCase

AF:

0.00589

EpiControl

AF:

0.00818

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Wagner syndrome

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Vitreoretinopathy

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

-0.71

CADD

Benign

0.57

(source)

DANN

Benign

0.49

PhyloP100

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=91/9

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over