rs741212

Positions:

• chr12-91180965-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001920.5(DCN):​c.-34+1690T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 152,250 control chromosomes in the GnomAD database, including 727 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 0.083 (727 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DCN NM_001920.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463

Genes affected

DCN (HGNC:2705): (decorin) This gene encodes a member of the small leucine-rich proteoglycan family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protein. This protein plays a role in collagen fibril assembly. Binding of this protein to multiple cell surface receptors mediates its role in tumor suppression, including a stimulatory effect on autophagy and inflammation and an inhibitory effect on angiogenesis and tumorigenesis. This gene and the related gene biglycan are thought to be the result of a gene duplication. Mutations in this gene are associated with congenital stromal corneal dystrophy in human patients. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -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 = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCN	NM_001920.5	c.-34+1690T>C		intron_variant		ENST00000052754.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCN	ENST00000052754.10	c.-34+1690T>C		intron_variant		1	NM_001920.5	P1

Frequencies

GnomAD3 genomes AF: 0.0830 AC: 12621 AN: 152132 Hom.: 728 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.109

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0829 AC: 12614 AN: 152250 Hom.: 727 Cov.: 32 AF XY: 0.0803 AC XY: 5976 AN XY: 74440

Gnomad4 AFR AF: 0.0210

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0298

Gnomad4 FIN AF: 0.0464

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.108

Alfa AF: 0.109 Hom.: 518

Bravo AF: 0.0852

Asia WGS AF: 0.0160 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.2
DANN	Benign	0.82

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: rs741212; hg19: chr12-91574742;