rs17205986

Positions:

• chr5-83564561-T-G

Variant summary

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

The NM_004385.5(VCAN):​c.9736-7855T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 152,298 control chromosomes in the GnomAD database, including 191 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 0.044 (191 hom., cov: 32)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCAN	NM_004385.5	c.9736-7855T>G		intron_variant		ENST00000265077.8
LOC124901021	XR_007058847.1	n.1218+1129T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAN	ENST00000265077.8	c.9736-7855T>G		intron_variant		1	NM_004385.5
VCAN-AS1	ENST00000513899.1	n.228+16532A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 6655 AN: 152182 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00951

Gnomad FIN AF: 0.0639

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0430

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

GnomAD4 genome AF: 0.0437 AC: 6658 AN: 152298 Hom.: 191 Cov.: 32 AF XY: 0.0426 AC XY: 3170 AN XY: 74462

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00931

Gnomad4 FIN AF: 0.0639

Gnomad4 NFE AF: 0.0673

Gnomad4 OTH AF: 0.0425

Alfa AF: 0.0600 Hom.: 39

Bravo AF: 0.0393

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.57

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: rs17205986; hg19: chr5-82860380;