12-91178638-C-T

Variant summary

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

The NM_001920.5(DCN):c.-33-53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 1,093,714 control chromosomes in the GnomAD database, including 6,029 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 0.13 (2026 hom., cov: 32)
  • Exomes 𝑓: 0.081 (4003 hom.)
• Consequence: DCN NM_001920.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCN	NM_001920.5	c.-33-53G>A		intron_variant		ENST00000052754.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCN	ENST00000052754.10	c.-33-53G>A		intron_variant		1	NM_001920.5	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20247 AN: 151764 Hom.: 2015 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.0806 AC: 75952 AN: 941832 Hom.: 4003 AF XY: 0.0792 AC XY: 38767 AN XY: 489334

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.0656

Gnomad4 FIN exome AF: 0.0456

Gnomad4 NFE exome AF: 0.0673

Gnomad4 OTH exome AF: 0.0934

GnomAD4 genome AF: 0.134 AC: 20293 AN: 151882 Hom.: 2026 Cov.: 32 AF XY: 0.130 AC XY: 9674 AN XY: 74224

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0673

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0691

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0919 Hom.: 875

Bravo AF: 0.147

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.21
Dann	Benign	0.45

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: rs3138167; hg19: chr12-91572415; COSMIC: COSV50007318; COSMIC: COSV50007318;