rs16900528

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.4569A>G(p.Thr1523Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 1,613,190 control chromosomes in the GnomAD database, including 5,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 448 hom., cov: 32)

Exomes 𝑓: 0.083 ( 5383 hom. )

Consequence

VCAN
NM_004385.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.102

Publications

10 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=-0.85).

BP6

Variant 5-83537572-A-G is Benign according to our data. Variant chr5-83537572-A-G is described in ClinVar as Benign. ClinVar VariationId is 259366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.102 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5 link	c.4569A>G	p.Thr1523Thr	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.4569A>G	p.Thr1523Thr	synonymous_variant	Exon 8 of 15	1	NM_004385.5	ENSP00000265077.3		P13611-1

Frequencies

GnomAD3 genomes

AF:

0.0687

AC:

10448

AN:

152112

Hom.:

448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.0570

Gnomad ASJ

AF:

0.0700

Gnomad EAS

AF:

0.0570

Gnomad SAS

AF:

0.0961

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0887

Gnomad OTH

AF:

0.0741

GnomAD2 exomes

AF:

0.0769

AC:

19217

AN:

249858

AF XY:

0.0789

show subpopulations

Gnomad AFR exome

AF:

0.0213

Gnomad AMR exome

AF:

0.0433

Gnomad ASJ exome

AF:

0.0636

Gnomad EAS exome

AF:

0.0545

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.0895

Gnomad OTH exome

AF:

0.0791

GnomAD4 exome

AF:

0.0834

AC:

121802

AN:

1460960

Hom.:

5383

Cov.:

AF XY:

0.0838

AC XY:

60878

AN XY:

726792

show subpopulations

African (AFR)

AF:

0.0192

AC:

641

AN:

33468

American (AMR)

AF:

0.0447

AC:

1996

AN:

44610

Ashkenazi Jewish (ASJ)

AF:

0.0634

AC:

1656

AN:

26116

East Asian (EAS)

AF:

0.0524

AC:

2079

AN:

39652

South Asian (SAS)

AF:

0.0910

AC:

7845

AN:

86244

European-Finnish (FIN)

AF:

0.110

AC:

5881

AN:

53364

Middle Eastern (MID)

AF:

0.0635

AC:

366

AN:

5764

European-Non Finnish (NFE)

AF:

0.0868

AC:

96452

AN:

1111396

Other (OTH)

AF:

0.0810

AC:

4886

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

6984

13968

20953

27937

34921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3484

6968

10452

13936

17420

<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:

0.0686

AC:

10450

AN:

152230

Hom.:

448

Cov.:

AF XY:

0.0700

AC XY:

5207

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0239

AC:

993

AN:

41552

American (AMR)

AF:

0.0569

AC:

869

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0700

AC:

243

AN:

3470

East Asian (EAS)

AF:

0.0570

AC:

295

AN:

5178

South Asian (SAS)

AF:

0.0954

AC:

460

AN:

4824

European-Finnish (FIN)

AF:

0.114

AC:

1211

AN:

10608

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0887

AC:

6032

AN:

68008

Other (OTH)

AF:

0.0766

AC:

162

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

489

978

1467

1956

2445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0774

Hom.:

423

Bravo

AF:

0.0596

Asia WGS

AF:

0.104

AC:

361

AN:

3478

EpiCase

AF:

0.0824

EpiControl

AF:

0.0829

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

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

- -

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

-0.85

CADD

Benign

1.2

(source)

DANN

Benign

0.66

PhyloP100

-0.10

Mutation Taster

=99/1

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