chr5-83547621-C-G

Variant names:

• chr5-83547621-C-G
• rs647873
• NM_004385.5:c.9380-350C>G

Variant summary

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

The NM_004385.5(VCAN):​c.9380-350C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,788 control chromosomes in the GnomAD database, including 24,279 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 0.56 (24279 hom., cov: 30)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5	c.9380-350C>G		intron_variant	Intron 9 of 14	ENST00000265077.8	NP_004376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8	c.9380-350C>G		intron_variant	Intron 9 of 14	1	NM_004385.5	ENSP00000265077.3

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85273 AN: 151670 Hom.: 24243 Cov.: 30

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.562 AC: 85362 AN: 151788 Hom.: 24279 Cov.: 30 AF XY: 0.561 AC XY: 41634 AN XY: 74150

African (AFR) AF: 0.639 AC: 26453 AN: 41370

American (AMR) AF: 0.565 AC: 8614 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2196 AN: 3462

East Asian (EAS) AF: 0.445 AC: 2284 AN: 5130

South Asian (SAS) AF: 0.436 AC: 2098 AN: 4808

European-Finnish (FIN) AF: 0.559 AC: 5886 AN: 10532

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35761 AN: 67930

Other (OTH) AF: 0.593 AC: 1249 AN: 2108

Alfa AF: 0.542 Hom.: 2704

Bravo AF: 0.567

Asia WGS AF: 0.454 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.59
DANN	Benign	0.35
PhyloP100		-1.0
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: rs647873; hg19: chr5-82843440; COSMIC: COSV54100956;