chr5-83539726-A-G

Variant names:

• chr5-83539726-A-G
• rs160279
• NM_004385.5:c.6723A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004385.5(VCAN):​c.6723A>G​(p.Arg2241Arg) 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 1,613,372 control chromosomes in the GnomAD database, including 190,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19064 hom., cov: 32)
  • Exomes 𝑓: 0.48 (171739 hom.)
• Consequence: VCAN NM_004385.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.423
• Publications: 24 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-83539726-A-G is Benign according to our data. Variant chr5-83539726-A-G is described in ClinVar as Benign. ClinVar VariationId is 198797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.423 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.516 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	NM_004385.5	MANE Select	c.6723A>G	p.Arg2241Arg	synonymous	Exon 8 of 15	NP_004376.2
	VCAN	NM_001164097.2		c.3762A>G	p.Arg1254Arg	synonymous	Exon 7 of 14	NP_001157569.1
	VCAN	NM_001164098.2		c.4004-5811A>G		intron	N/A	NP_001157570.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	ENST00000265077.8	TSL:1 MANE Select	c.6723A>G	p.Arg2241Arg	synonymous	Exon 8 of 15	ENSP00000265077.3
	VCAN	ENST00000343200.9	TSL:1	c.3762A>G	p.Arg1254Arg	synonymous	Exon 7 of 14	ENSP00000340062.5
	VCAN	ENST00000513016.5	TSL:1	n.4113A>G		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75894 AN: 151866 Hom.: 19051 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.535

GnomAD2 exomes AF: 0.485 AC: 121044 AN: 249592 AF XY: 0.479

Gnomad AFR exome AF: 0.504

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.576

Gnomad EAS exome AF: 0.399

Gnomad FIN exome AF: 0.513

Gnomad NFE exome AF: 0.498

Gnomad OTH exome AF: 0.495

GnomAD4 exome AF: 0.484 AC: 707047 AN: 1461386 Hom.: 171739 Cov.: 72 AF XY: 0.481 AC XY: 349651 AN XY: 726978

African (AFR) AF: 0.499 AC: 16694 AN: 33476

American (AMR) AF: 0.518 AC: 23159 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 15016 AN: 26128

East Asian (EAS) AF: 0.463 AC: 18370 AN: 39664

South Asian (SAS) AF: 0.389 AC: 33589 AN: 86256

European-Finnish (FIN) AF: 0.508 AC: 26966 AN: 53100

Middle Eastern (MID) AF: 0.503 AC: 2899 AN: 5768

European-Non Finnish (NFE) AF: 0.487 AC: 541346 AN: 1111942

Other (OTH) AF: 0.480 AC: 29008 AN: 60378

GnomAD4 genome AF: 0.500 AC: 75941 AN: 151986 Hom.: 19064 Cov.: 32 AF XY: 0.499 AC XY: 37045 AN XY: 74264

African (AFR) AF: 0.504 AC: 20879 AN: 41422

American (AMR) AF: 0.526 AC: 8030 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2021 AN: 3472

East Asian (EAS) AF: 0.409 AC: 2108 AN: 5150

South Asian (SAS) AF: 0.392 AC: 1889 AN: 4820

European-Finnish (FIN) AF: 0.529 AC: 5594 AN: 10574

Middle Eastern (MID) AF: 0.500 AC: 145 AN: 290

European-Non Finnish (NFE) AF: 0.493 AC: 33525 AN: 67972

Other (OTH) AF: 0.536 AC: 1131 AN: 2112

Alfa AF: 0.500 Hom.: 14855

Bravo AF: 0.499

Asia WGS AF: 0.411 AC: 1426 AN: 3478

EpiCase AF: 0.502

EpiControl AF: 0.503

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Wagner disease Benign:3

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

not specified Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jun 12, 2014

Eurofins Ntd Llc (ga)

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

Sep 01, 2020

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs160279; hg19: chr5-82835545; COSMIC: COSV54100118; COSMIC: COSV54100118;