5-83472395-G-T

Variant names:

• chr5-83472395-G-T
• rs962066
• NM_004385.5:c.-7+372G>T

Variant summary

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

The NM_004385.5(VCAN):​c.-7+372G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,796 control chromosomes in the GnomAD database, including 6,435 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 0.27 (6435 hom., cov: 31)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• 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 Gene-Disease associations (from GenCC):

• Wagner disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

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 (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5	c.-7+372G>T		intron_variant	Intron 1 of 14	ENST00000265077.8	NP_004376.2
VCAN	NM_001164097.2	c.-7+372G>T		intron_variant	Intron 1 of 13		NP_001157569.1
VCAN	NM_001164098.2	c.-7+372G>T		intron_variant	Intron 1 of 13		NP_001157570.1
VCAN	NM_001126336.3	c.-7+372G>T		intron_variant	Intron 1 of 12		NP_001119808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8	c.-7+372G>T		intron_variant	Intron 1 of 14	1	NM_004385.5	ENSP00000265077.3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41698 AN: 151678 Hom.: 6441 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.275 AC: 41694 AN: 151796 Hom.: 6435 Cov.: 31 AF XY: 0.272 AC XY: 20201 AN XY: 74176

African (AFR) AF: 0.132 AC: 5491 AN: 41460

American (AMR) AF: 0.311 AC: 4745 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1076 AN: 3462

East Asian (EAS) AF: 0.130 AC: 672 AN: 5172

South Asian (SAS) AF: 0.222 AC: 1062 AN: 4790

European-Finnish (FIN) AF: 0.326 AC: 3424 AN: 10496

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24175 AN: 67836

Other (OTH) AF: 0.282 AC: 593 AN: 2104

Alfa AF: 0.297 Hom.: 3809

Bravo AF: 0.269

Asia WGS AF: 0.202 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.53
PhyloP100		-0.022
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs962066; hg19: chr5-82768214;