5-83538811-T-C

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.5808T>C(p.Gly1936Gly) 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 1,613,530 control chromosomes in the GnomAD database, including 190,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19150 hom., cov: 32)

Exomes 𝑓: 0.48 ( 171819 hom. )

Consequence

VCAN
NM_004385.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0340

Publications

22 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 links:

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

VCAN-AS1 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=-0.6).

BP6

Variant 5-83538811-T-C is Benign according to our data. Variant chr5-83538811-T-C is described in ClinVar as Benign. ClinVar VariationId is 167824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.034 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5 link	c.5808T>C	p.Gly1936Gly	synonymous_variant	Exon 8 of 15	ENST00000265077.8	NP_004376.2	P13611-1A0A024RAQ9Q59FG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8 link	c.5808T>C	p.Gly1936Gly	synonymous_variant	Exon 8 of 15	1	NM_004385.5	ENSP00000265077.3		P13611-1

Frequencies

GnomAD3 genomes

AF:

0.501

AC:

76012

AN:

151836

Hom.:

19137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.507

Gnomad AMI

AF:

0.680

Gnomad AMR

AF:

0.526

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.410

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.536

GnomAD2 exomes

AF:

0.485

AC:

121638

AN:

250688

AF XY:

0.479

show subpopulations

Gnomad AFR exome

AF:

0.506

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.398

Gnomad FIN exome

AF:

0.513

Gnomad NFE exome

AF:

0.499

Gnomad OTH exome

AF:

0.495

GnomAD4 exome

AF:

0.484

AC:

707184

AN:

1461576

Hom.:

171819

Cov.:

AF XY:

0.481

AC XY:

349669

AN XY:

727102

show subpopulations

African (AFR)

AF:

0.499

AC:

16716

AN:

33476

American (AMR)

AF:

0.519

AC:

23176

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.575

AC:

15018

AN:

26132

East Asian (EAS)

AF:

0.463

AC:

18384

AN:

39696

South Asian (SAS)

AF:

0.388

AC:

33471

AN:

86258

European-Finnish (FIN)

AF:

0.508

AC:

27036

AN:

53246

Middle Eastern (MID)

AF:

0.502

AC:

2897

AN:

5768

European-Non Finnish (NFE)

AF:

0.487

AC:

541479

AN:

1111914

Other (OTH)

AF:

0.480

AC:

29007

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

26504

53008

79511

106015

132519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15876

31752

47628

63504

79380

<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:

0.501

AC:

76059

AN:

151954

Hom.:

19150

Cov.:

AF XY:

0.500

AC XY:

37117

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.507

AC:

21007

AN:

41466

American (AMR)

AF:

0.526

AC:

8031

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

2021

AN:

3468

East Asian (EAS)

AF:

0.410

AC:

2110

AN:

5148

South Asian (SAS)

AF:

0.391

AC:

1883

AN:

4814

European-Finnish (FIN)

AF:

0.529

AC:

5579

AN:

10542

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.494

AC:

33530

AN:

67938

Other (OTH)

AF:

0.536

AC:

1133

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1959

3917

5876

7834

9793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.503

Hom.:

29336

Bravo

AF:

0.499

Asia WGS

AF:

0.412

AC:

1431

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

Dec 05, 2021

Genome-Nilou Lab

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

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Jan 20, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 05, 2021

GeneDx

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

-0.60

CADD

Benign

6.7

(source)

DANN

Benign

0.83

PhyloP100

0.034

Mutation Taster

=92/8

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