rs16900528

Variant names:

• chr5-83537572-A-G
• rs16900528
• NM_004385.5:c.4569A>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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.102
• Publications: 10 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=-0.85).
• 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.

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.4569A>G	p.Thr1523Thr	synonymous	Exon 8 of 15	NP_004376.2
	VCAN	NM_001164097.2		c.1608A>G	p.Thr536Thr	synonymous	Exon 7 of 14	NP_001157569.1
	VCAN	NM_001164098.2		c.4004-7965A>G		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.4569A>G	p.Thr1523Thr	synonymous	Exon 8 of 15	ENSP00000265077.3
	VCAN	ENST00000343200.9	TSL:1	c.1608A>G	p.Thr536Thr	synonymous	Exon 7 of 14	ENSP00000340062.5
	VCAN	ENST00000513960.5	TSL:1	c.1608A>G	p.Thr536Thr	synonymous	Exon 7 of 7	ENSP00000426251.1

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10448 AN: 152112 Hom.: 448 Cov.: 32

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

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.: 72 AF XY: 0.0838 AC XY: 60878 AN XY: 726792

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

GnomAD4 genome AF: 0.0686 AC: 10450 AN: 152230 Hom.: 448 Cov.: 32 AF XY: 0.0700 AC XY: 5207 AN XY: 74426

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: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0887 AC: 6032 AN: 68008

Other (OTH) AF: 0.0766 AC: 162 AN: 2114

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-0.10
Mutation Taster		=99/1	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: rs16900528; hg19: chr5-82833391; COSMIC: COSV54104747; COSMIC: COSV54104747;