5-83471911-A-C

Variant names:

• chr5-83471911-A-C
• rs557823406
• NM_004385.5:c.-119A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004385.5(VCAN):​c.-119A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000445 in 393,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (0 hom.)
• Consequence: VCAN NM_004385.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 1.79
• Publications: 0 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 Gene-Disease associations (from GenCC):

• Wagner disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-83471911-A-C is Benign according to our data. Variant chr5-83471911-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 354385.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000348 (53/152138) while in subpopulation SAS AF = 0.00146 (7/4800). AF 95% confidence interval is 0.000684. There are 0 homozygotes in GnomAd4. There are 27 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 53 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	NM_004385.5	MANE Select	c.-119A>C		5_prime_UTR	Exon 1 of 15	NP_004376.2
	VCAN	NM_001164097.2		c.-119A>C		5_prime_UTR	Exon 1 of 14	NP_001157569.1	P13611-2
	VCAN	NM_001164098.2		c.-119A>C		5_prime_UTR	Exon 1 of 14	NP_001157570.1	P13611-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	ENST00000265077.8	TSL:1 MANE Select	c.-119A>C		5_prime_UTR	Exon 1 of 15	ENSP00000265077.3	P13611-1
	VCAN	ENST00000343200.9	TSL:1	c.-119A>C		5_prime_UTR	Exon 1 of 14	ENSP00000340062.5	P13611-2
	VCAN	ENST00000342785.8	TSL:1	c.-119A>C		5_prime_UTR	Exon 1 of 14	ENSP00000342768.4	P13611-3

Frequencies

GnomAD3 genomes AF: 0.000349 AC: 53 AN: 152020 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00192

GnomAD4 exome AF: 0.000505 AC: 122 AN: 241544 Hom.: 0 Cov.: 0 AF XY: 0.000538 AC XY: 66 AN XY: 122656

African (AFR) AF: 0.000283 AC: 2 AN: 7072

American (AMR) AF: 0.000275 AC: 2 AN: 7282

Ashkenazi Jewish (ASJ) AF: 0.00759 AC: 69 AN: 9092

East Asian (EAS) AF: 0.00 AC: 0 AN: 22654

South Asian (SAS) AF: 0.00177 AC: 4 AN: 2258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20324

Middle Eastern (MID) AF: 0.000785 AC: 1 AN: 1274

European-Non Finnish (NFE) AF: 0.000193 AC: 30 AN: 155514

Other (OTH) AF: 0.000871 AC: 14 AN: 16074

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74356

African (AFR) AF: 0.0000482 AC: 2 AN: 41518

American (AMR) AF: 0.000523 AC: 8 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00146 AC: 7 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67984

Other (OTH) AF: 0.00190 AC: 4 AN: 2106

Alfa AF: 0.000159 Hom.: 0

Bravo AF: 0.000374

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	Wagner disease (2)
-	-	1	Vitreoretinopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.58
PhyloP100		1.8
PromoterAI		0.12	Neutral

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: rs557823406; hg19: chr5-82767730;