NM_004385.5:c.9493+825T>C

Variant names:

• chr5-83548909-T-C
• rs309596
• NM_004385.5:c.9493+825T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004385.5(VCAN):​c.9493+825T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,192 control chromosomes in the GnomAD database, including 49,818 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (49818 hom., cov: 33)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 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.9493+825T>C		intron	N/A	NP_004376.2
	VCAN	NM_001164097.2		c.6532+825T>C		intron	N/A	NP_001157569.1
	VCAN	NM_001164098.2		c.4231+825T>C		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.9493+825T>C		intron	N/A	ENSP00000265077.3
	VCAN	ENST00000343200.9	TSL:1	c.6532+825T>C		intron	N/A	ENSP00000340062.5
	VCAN	ENST00000342785.8	TSL:1	c.4231+825T>C		intron	N/A	ENSP00000342768.4

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122475 AN: 152074 Hom.: 49758 Cov.: 33

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.813

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.806 AC: 122595 AN: 152192 Hom.: 49818 Cov.: 33 AF XY: 0.798 AC XY: 59348 AN XY: 74392

African (AFR) AF: 0.882 AC: 36659 AN: 41542

American (AMR) AF: 0.844 AC: 12911 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2744 AN: 3468

East Asian (EAS) AF: 0.591 AC: 3056 AN: 5168

South Asian (SAS) AF: 0.564 AC: 2722 AN: 4822

European-Finnish (FIN) AF: 0.764 AC: 8074 AN: 10572

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53728 AN: 68008

Other (OTH) AF: 0.812 AC: 1715 AN: 2112

Alfa AF: 0.798 Hom.: 153062

Bravo AF: 0.820

Asia WGS AF: 0.619 AC: 2153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.16
DANN	Benign	0.46
PhyloP100		-0.89
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: rs309596; hg19: chr5-82844728;