rs2548541

Variant names:

• chr5-83537326-G-A
• rs2548541
• NM_004385.5:c.4323G>A

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.4323G>A​(p.Gln1441Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 1,613,732 control chromosomes in the GnomAD database, including 315,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35430 hom., cov: 32)
  • Exomes 𝑓: 0.62 (280193 hom.)
• Consequence: VCAN NM_004385.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.634
• Publications: 22 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=-0.68).
• BP6: Variant 5-83537326-G-A is Benign according to our data. Variant chr5-83537326-G-A is described in ClinVar as Benign. ClinVar VariationId is 198803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.634 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	NM_004385.5	MANE Select	c.4323G>A	p.Gln1441Gln	synonymous	Exon 8 of 15	NP_004376.2
	VCAN	NM_001164097.2		c.1362G>A	p.Gln454Gln	synonymous	Exon 7 of 14	NP_001157569.1
	VCAN	NM_001164098.2		c.4004-8211G>A		intron	N/A	NP_001157570.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	ENST00000265077.8	TSL:1 MANE Select	c.4323G>A	p.Gln1441Gln	synonymous	Exon 8 of 15	ENSP00000265077.3
	VCAN	ENST00000343200.9	TSL:1	c.1362G>A	p.Gln454Gln	synonymous	Exon 7 of 14	ENSP00000340062.5
	VCAN	ENST00000513960.5	TSL:1	c.1362G>A	p.Gln454Gln	synonymous	Exon 7 of 7	ENSP00000426251.1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102774 AN: 151908 Hom.: 35382 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.698

GnomAD2 exomes AF: 0.643 AC: 161062 AN: 250626 AF XY: 0.644

Gnomad AFR exome AF: 0.808

Gnomad AMR exome AF: 0.589

Gnomad ASJ exome AF: 0.715

Gnomad EAS exome AF: 0.629

Gnomad FIN exome AF: 0.654

Gnomad NFE exome AF: 0.613

Gnomad OTH exome AF: 0.638

GnomAD4 exome AF: 0.617 AC: 902380 AN: 1461702 Hom.: 280193 Cov.: 87 AF XY: 0.620 AC XY: 450726 AN XY: 727148

African (AFR) AF: 0.813 AC: 27196 AN: 33466

American (AMR) AF: 0.594 AC: 26521 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 18570 AN: 26130

East Asian (EAS) AF: 0.658 AC: 26127 AN: 39696

South Asian (SAS) AF: 0.702 AC: 60573 AN: 86258

European-Finnish (FIN) AF: 0.648 AC: 34601 AN: 53402

Middle Eastern (MID) AF: 0.699 AC: 4030 AN: 5768

European-Non Finnish (NFE) AF: 0.599 AC: 666428 AN: 1111924

Other (OTH) AF: 0.635 AC: 38334 AN: 60388

GnomAD4 genome AF: 0.677 AC: 102877 AN: 152030 Hom.: 35430 Cov.: 32 AF XY: 0.681 AC XY: 50569 AN XY: 74292

African (AFR) AF: 0.805 AC: 33410 AN: 41492

American (AMR) AF: 0.623 AC: 9506 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2468 AN: 3466

East Asian (EAS) AF: 0.635 AC: 3274 AN: 5156

South Asian (SAS) AF: 0.719 AC: 3462 AN: 4818

European-Finnish (FIN) AF: 0.669 AC: 7066 AN: 10568

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41355 AN: 67958

Other (OTH) AF: 0.698 AC: 1473 AN: 2110

Alfa AF: 0.636 Hom.: 51514

Bravo AF: 0.674

Asia WGS AF: 0.663 AC: 2303 AN: 3478

EpiCase AF: 0.622

EpiControl AF: 0.623

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Wagner disease (3)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Vitreoretinopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.14
DANN	Benign	0.81
PhyloP100		-0.63
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: rs2548541; hg19: chr5-82833145; COSMIC: COSV54100085; COSMIC: COSV54100085;