5-83471911-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004385.5(VCAN):​c.-119A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 241,544 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: VCAN NM_004385.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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>T		5_prime_UTR	Exon 1 of 15	NP_004376.2
	VCAN	NM_001164097.2		c.-119A>T		5_prime_UTR	Exon 1 of 14	NP_001157569.1	P13611-2
	VCAN	NM_001164098.2		c.-119A>T		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>T		5_prime_UTR	Exon 1 of 15	ENSP00000265077.3	P13611-1
	VCAN	ENST00000343200.9	TSL:1	c.-119A>T		5_prime_UTR	Exon 1 of 14	ENSP00000340062.5	P13611-2
	VCAN	ENST00000342785.8	TSL:1	c.-119A>T		5_prime_UTR	Exon 1 of 14	ENSP00000342768.4	P13611-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000414 AC: 1 AN: 241544 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 122656

African (AFR) AF: 0.00 AC: 0 AN: 7072

American (AMR) AF: 0.00 AC: 0 AN: 7282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9092

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 2258

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1274

European-Non Finnish (NFE) AF: 0.00000643 AC: 1 AN: 155514

Other (OTH) AF: 0.00 AC: 0 AN: 16074

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		1.8
PromoterAI		0.22	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;