chr5-83514895-A-G

Variant names:

• chr5-83514895-A-G
• rs160380
• NM_004385.5:c.1042+2499A>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.1042+2499A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,146 control chromosomes in the GnomAD database, including 10,589 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 0.37 (10589 hom., cov: 33)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5	c.1042+2499A>G		intron_variant	Intron 6 of 14	ENST00000265077.8	NP_004376.2
VCAN	NM_001164097.2	c.1042+2499A>G		intron_variant	Intron 6 of 13		NP_001157569.1
VCAN	NM_001164098.2	c.1042+2499A>G		intron_variant	Intron 6 of 13		NP_001157570.1
VCAN	NM_001126336.3	c.1042+2499A>G		intron_variant	Intron 6 of 12		NP_001119808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8	c.1042+2499A>G		intron_variant	Intron 6 of 14	1	NM_004385.5	ENSP00000265077.3

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55709 AN: 152028 Hom.: 10585 Cov.: 33

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.366 AC: 55742 AN: 152146 Hom.: 10589 Cov.: 33 AF XY: 0.370 AC XY: 27526 AN XY: 74392

African (AFR) AF: 0.388 AC: 16087 AN: 41504

American (AMR) AF: 0.449 AC: 6868 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1515 AN: 3464

East Asian (EAS) AF: 0.574 AC: 2964 AN: 5160

South Asian (SAS) AF: 0.426 AC: 2051 AN: 4818

European-Finnish (FIN) AF: 0.313 AC: 3315 AN: 10584

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.318 AC: 21636 AN: 68002

Other (OTH) AF: 0.393 AC: 831 AN: 2116

Alfa AF: 0.349 Hom.: 28643

Bravo AF: 0.380

Asia WGS AF: 0.489 AC: 1704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		1.7
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: rs160380; hg19: chr5-82810714;