rs16900564

Variant names:

• chr5-83553500-C-T
• rs16900564
• NM_004385.5:c.9630C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-83553500-C-T
• chr5-83553500-C-A
• chr5-83553500-C-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.9630C>T​(p.His3210His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00939 in 1,614,008 control chromosomes in the GnomAD database, including 1,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (647 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (618 hom.)
• Consequence: VCAN NM_004385.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -4.50
• Publications: 1 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=-0.57).
• BP6: Variant 5-83553500-C-T is Benign according to our data. Variant chr5-83553500-C-T is described in ClinVar as Benign. ClinVar VariationId is 259378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 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.9630C>T	p.His3210His	synonymous	Exon 11 of 15	NP_004376.2
	VCAN	NM_001164097.2		c.6669C>T	p.His2223His	synonymous	Exon 10 of 14	NP_001157569.1	P13611-2
	VCAN	NM_001164098.2		c.4368C>T	p.His1456His	synonymous	Exon 10 of 14	NP_001157570.1	P13611-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	ENST00000265077.8	TSL:1 MANE Select	c.9630C>T	p.His3210His	synonymous	Exon 11 of 15	ENSP00000265077.3	P13611-1
	VCAN	ENST00000343200.9	TSL:1	c.6669C>T	p.His2223His	synonymous	Exon 10 of 14	ENSP00000340062.5	P13611-2
	VCAN	ENST00000342785.8	TSL:1	c.4368C>T	p.His1456His	synonymous	Exon 10 of 14	ENSP00000342768.4	P13611-3

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7509 AN: 152112 Hom.: 646 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0354

GnomAD2 exomes AF: 0.0133 AC: 3330 AN: 250994 AF XY: 0.00947

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.00879

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000520

Gnomad OTH exome AF: 0.00751

GnomAD4 exome AF: 0.00521 AC: 7621 AN: 1461778 Hom.: 618 Cov.: 32 AF XY: 0.00440 AC XY: 3203 AN XY: 727196

African (AFR) AF: 0.183 AC: 6138 AN: 33474

American (AMR) AF: 0.00973 AC: 435 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39684

South Asian (SAS) AF: 0.000441 AC: 38 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00868 AC: 50 AN: 5762

European-Non Finnish (NFE) AF: 0.000273 AC: 304 AN: 1111936

Other (OTH) AF: 0.0108 AC: 653 AN: 60390

GnomAD4 genome AF: 0.0495 AC: 7530 AN: 152230 Hom.: 647 Cov.: 33 AF XY: 0.0476 AC XY: 3546 AN XY: 74430

African (AFR) AF: 0.173 AC: 7176 AN: 41526

American (AMR) AF: 0.0157 AC: 240 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68030

Other (OTH) AF: 0.0351 AC: 74 AN: 2110

Alfa AF: 0.0187 Hom.: 306

Bravo AF: 0.0560

Asia WGS AF: 0.00953 AC: 34 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

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	-0.57
CADD	Benign	0.73
DANN	Benign	0.90
PhyloP100		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=88/12	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: rs16900564; hg19: chr5-82849319; COSMIC: COSV54107006; COSMIC: COSV54107006;