chr5-83564561-T-G

Variant names:

• chr5-83564561-T-G
• rs17205986
• NM_004385.5:c.9736-7855T>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.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
• Publications: 3 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)

LOC124901021 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004385.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	NM_004385.5	MANE Select	c.9736-7855T>G		intron	N/A	NP_004376.2
	VCAN	NM_001164097.2		c.6775-7855T>G		intron	N/A	NP_001157569.1
	VCAN	NM_001164098.2		c.4474-7855T>G		intron	N/A	NP_001157570.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	ENST00000265077.8	TSL:1 MANE Select	c.9736-7855T>G		intron	N/A	ENSP00000265077.3
	VCAN	ENST00000343200.9	TSL:1	c.6775-7855T>G		intron	N/A	ENSP00000340062.5
	VCAN	ENST00000342785.8	TSL:1	c.4474-7855T>G		intron	N/A	ENSP00000342768.4

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

African (AFR) AF: 0.0122 AC: 506 AN: 41576

American (AMR) AF: 0.0439 AC: 672 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00931 AC: 45 AN: 4834

European-Finnish (FIN) AF: 0.0639 AC: 678 AN: 10612

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0673 AC: 4575 AN: 67996

Other (OTH) AF: 0.0425 AC: 90 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.57
PhyloP100		-0.20
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: rs17205986; hg19: chr5-82860380;