5-83489922-G-T

Position:

• chr5-83489922-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004385.5(VCAN):​c.71-176G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,600 control chromosomes in the GnomAD database, including 11,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (11815 hom., cov: 31)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0600

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-83489922-G-T is Benign according to our data. Variant chr5-83489922-G-T is described in ClinVar as [Benign]. Clinvar id is 1227255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCAN	NM_004385.5	c.71-176G>T		intron_variant		ENST00000265077.8
VCAN	NM_001126336.3	c.71-176G>T		intron_variant
VCAN	NM_001164097.2	c.71-176G>T		intron_variant
VCAN	NM_001164098.2	c.71-176G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAN	ENST00000265077.8	c.71-176G>T		intron_variant		1	NM_004385.5

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59088 AN: 151484 Hom.: 11816 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.390 AC: 59119 AN: 151600 Hom.: 11815 Cov.: 31 AF XY: 0.387 AC XY: 28624 AN XY: 74042

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.372

Alfa AF: 0.387 Hom.: 1451

Bravo AF: 0.397

Asia WGS AF: 0.232 AC: 809 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.58

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: rs4339334; hg19: chr5-82785741;