rs80200229

Variant names:

• chr5-83539240-G-A
• rs80200229
• NM_004385.5:c.6237G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-83539240-G-A
• chr5-83539240-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004385.5(VCAN):​c.6237G>A​(p.Lys2079Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,614,038 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (49 hom.)
• Consequence: VCAN NM_004385.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.130
• Publications: 2 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)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-83539240-G-A is Benign according to our data. Variant chr5-83539240-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.13 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0118 (1803/152300) while in subpopulation AFR AF = 0.0411 (1707/41546). AF 95% confidence interval is 0.0395. There are 36 homozygotes in GnomAd4. There are 857 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1803 AD gene.

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.6237G>A	p.Lys2079Lys	synonymous	Exon 8 of 15	NP_004376.2
	VCAN	NM_001164097.2		c.3276G>A	p.Lys1092Lys	synonymous	Exon 7 of 14	NP_001157569.1
	VCAN	NM_001164098.2		c.4004-6297G>A		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.6237G>A	p.Lys2079Lys	synonymous	Exon 8 of 15	ENSP00000265077.3
	VCAN	ENST00000343200.9	TSL:1	c.3276G>A	p.Lys1092Lys	synonymous	Exon 7 of 14	ENSP00000340062.5
	VCAN	ENST00000513960.5	TSL:1	c.3276G>A	p.Lys1092Lys	synonymous	Exon 7 of 7	ENSP00000426251.1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1790 AN: 152182 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00290 AC: 727 AN: 250716 AF XY: 0.00218

Gnomad AFR exome AF: 0.0410

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00126 AC: 1847 AN: 1461738 Hom.: 49 Cov.: 79 AF XY: 0.00112 AC XY: 814 AN XY: 727154

African (AFR) AF: 0.0448 AC: 1500 AN: 33476

American (AMR) AF: 0.00193 AC: 86 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5766

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111954

Other (OTH) AF: 0.00305 AC: 184 AN: 60394

GnomAD4 genome AF: 0.0118 AC: 1803 AN: 152300 Hom.: 36 Cov.: 32 AF XY: 0.0115 AC XY: 857 AN XY: 74464

African (AFR) AF: 0.0411 AC: 1707 AN: 41546

American (AMR) AF: 0.00516 AC: 79 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68038

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00562 Hom.: 7

Bravo AF: 0.0143

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Wagner disease (2)
-	-	1	not specified (1)
-	-	1	Vitreoretinopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.61
DANN	Benign	0.58
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

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: rs80200229; hg19: chr5-82835059;