rs113014073

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004385.5(VCAN):c.9075G>A(p.Thr3025=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,613,704 control chromosomes in the GnomAD database, including 1,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 87 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1130 hom. )

Consequence

VCAN
NM_004385.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.307

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=-0.78).

BP6

Variant 5-83542078-G-A is Benign according to our data. Variant chr5-83542078-G-A is described in ClinVar as [Benign]. Clinvar id is 259375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-83542078-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.307 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0276 (4203/152248) while in subpopulation NFE AF= 0.0387 (2635/68014). AF 95% confidence interval is 0.0375. There are 87 homozygotes in gnomad4. There are 2020 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4203 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCAN	NM_004385.5 linkuse as main transcript	c.9075G>A	p.Thr3025=	synonymous_variant	8/15	ENST00000265077.8	NP_004376.2
VCAN-AS1	NR_136215.1 linkuse as main transcript	n.285-7905C>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.9075G>A	p.Thr3025=	synonymous_variant	8/15	1	NM_004385.5	ENSP00000265077		P13611-1
VCAN-AS1	ENST00000513899.1 linkuse as main transcript	n.229-377C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4207

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00702

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0305

Gnomad ASJ

AF:

0.0859

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.0315

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0388

Gnomad OTH

AF:

0.0350

GnomAD3 exomes

AF:

0.0305

AC:

7655

AN:

250712

Hom.:

164

AF XY:

0.0314

AC XY:

4259

AN XY:

135456

show subpopulations

Gnomad AFR exome

AF:

0.00628

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.0791

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.0331

Gnomad NFE exome

AF:

0.0412

Gnomad OTH exome

AF:

0.0435

GnomAD4 exome

AF:

0.0359

AC:

52450

AN:

1461456

Hom.:

1130

Cov.:

AF XY:

0.0356

AC XY:

25883

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.00666

Gnomad4 AMR exome

AF:

0.0222

Gnomad4 ASJ exome

AF:

0.0800

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0138

Gnomad4 FIN exome

AF:

0.0314

Gnomad4 NFE exome

AF:

0.0395

Gnomad4 OTH exome

AF:

0.0352

GnomAD4 genome

AF:

0.0276

AC:

4203

AN:

152248

Hom.:

Cov.:

AF XY:

0.0271

AC XY:

2020

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00700

Gnomad4 AMR

AF:

0.0304

Gnomad4 ASJ

AF:

0.0859

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.0315

Gnomad4 NFE

AF:

0.0387

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0372

Hom.:

Bravo

AF:

0.0265

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0444

EpiControl

AF:

0.0445

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Wagner syndrome

Benign:2

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	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Vitreoretinopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.65

DANN

Benign

0.38

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