dbSNP rs11726: VCAN:c.*1429A>G (chr5-83581863-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004385.5(VCAN):c.*1429A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,892 control chromosomes in the GnomAD database, including 23,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.55 ( 23495 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

VCAN
NM_004385.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 2.63

Publications

6 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: G2P, Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

VCAN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-83581863-A-G is Benign according to our data. Variant chr5-83581863-A-G is described in ClinVar as Benign. ClinVar VariationId is 354492.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004385.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VCAN	NM_004385.5	MANE Select	c.*1429A>G	3_prime_UTR	Exon 15 of 15	NP_004376.2
VCAN	NM_001164097.2		c.*1429A>G	3_prime_UTR	Exon 14 of 14	NP_001157569.1	P13611-2
VCAN	NM_001164098.2		c.*1429A>G	3_prime_UTR	Exon 14 of 14	NP_001157570.1	P13611-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VCAN	ENST00000265077.8	TSL:1 MANE Select	c.*1429A>G	3_prime_UTR	Exon 15 of 15	ENSP00000265077.3	P13611-1
VCAN	ENST00000343200.9	TSL:1	c.*1429A>G	3_prime_UTR	Exon 14 of 14	ENSP00000340062.5	P13611-2
VCAN	ENST00000342785.8	TSL:1	c.*1429A>G	3_prime_UTR	Exon 14 of 14	ENSP00000342768.4	P13611-3

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

83973

AN:

151774

Hom.:

23484

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.850

Gnomad AMR

AF:

0.667

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.576

Gnomad FIN

AF:

0.530

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.563

Gnomad OTH

AF:

0.584

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.553

AC:

84020

AN:

151892

Hom.:

23495

Cov.:

AF XY:

0.554

AC XY:

41152

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.479

AC:

19843

AN:

41442

American (AMR)

AF:

0.667

AC:

10185

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

2102

AN:

3470

East Asian (EAS)

AF:

0.613

AC:

3158

AN:

5154

South Asian (SAS)

AF:

0.574

AC:

2765

AN:

4816

European-Finnish (FIN)

AF:

0.530

AC:

5580

AN:

10526

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.563

AC:

38214

AN:

67910

Other (OTH)

AF:

0.588

AC:

1239

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1934

3869

5803

7738

9672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.537

Hom.:

2782

Bravo

AF:

0.560

Asia WGS

AF:

0.610

AC:

2114

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Wagner disease (2)

Vitreoretinopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

8.7

(source)

DANN

Benign

0.64

PhyloP100

2.6

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over