5-83566408-T-C

Variant names:

• chr5-83566408-T-C
• rs160187
• NM_004385.5:c.9736-6008T>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.9736-6008T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,130 control chromosomes in the GnomAD database, including 51,507 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 0.82 (51507 hom., cov: 33)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 4 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)

LOC124901021 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 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.9736-6008T>C		intron	N/A	NP_004376.2
	VCAN	NM_001164097.2		c.6775-6008T>C		intron	N/A	NP_001157569.1	P13611-2
	VCAN	NM_001164098.2		c.4474-6008T>C		intron	N/A	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.9736-6008T>C		intron	N/A	ENSP00000265077.3	P13611-1
	VCAN	ENST00000343200.9	TSL:1	c.6775-6008T>C		intron	N/A	ENSP00000340062.5	P13611-2
	VCAN	ENST00000342785.8	TSL:1	c.4474-6008T>C		intron	N/A	ENSP00000342768.4	P13611-3

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124690 AN: 152006 Hom.: 51442 Cov.: 33

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.820 AC: 124817 AN: 152130 Hom.: 51507 Cov.: 33 AF XY: 0.822 AC XY: 61117 AN XY: 74350

African (AFR) AF: 0.898 AC: 37292 AN: 41510

American (AMR) AF: 0.836 AC: 12766 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2584 AN: 3472

East Asian (EAS) AF: 0.815 AC: 4215 AN: 5172

South Asian (SAS) AF: 0.826 AC: 3985 AN: 4824

European-Finnish (FIN) AF: 0.796 AC: 8410 AN: 10566

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.779 AC: 52980 AN: 67994

Other (OTH) AF: 0.816 AC: 1724 AN: 2112

Alfa AF: 0.792 Hom.: 179360

Bravo AF: 0.828

Asia WGS AF: 0.808 AC: 2810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.50
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: rs160187; hg19: chr5-82862227;