chr5-83543755-T-A

Position:

• chr5-83543755-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004385.5(VCAN):​c.9265+1487T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 152,212 control chromosomes in the GnomAD database, including 57,787 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 0.87 (57787 hom., cov: 33)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCAN	NM_004385.5	c.9265+1487T>A		intron_variant		ENST00000265077.8
VCAN-AS1	NR_136215.1	n.285-9582A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAN	ENST00000265077.8	c.9265+1487T>A		intron_variant		1	NM_004385.5
VCAN-AS1	ENST00000513899.1	n.229-2054A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132461 AN: 152094 Hom.: 57729 Cov.: 33

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.884

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

GnomAD4 genome AF: 0.871 AC: 132577 AN: 152212 Hom.: 57787 Cov.: 33 AF XY: 0.870 AC XY: 64722 AN XY: 74394

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.887

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.874

Gnomad4 NFE AF: 0.871

Gnomad4 OTH AF: 0.883

Alfa AF: 0.878 Hom.: 7298

Bravo AF: 0.873

Asia WGS AF: 0.814 AC: 2828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs2445874; hg19: chr5-82839574;