rs516115

Positions:

• chr12-91163515-T-C
• chr12-91163515-T-G

Variant summary

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

The NM_001920.5(DCN):​c.324+1090A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,988 control chromosomes in the GnomAD database, including 12,919 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 0.38 (12919 hom., cov: 31)
• Consequence: DCN NM_001920.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.945

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCN	NM_001920.5	c.324+1090A>G		intron_variant		ENST00000052754.10	NP_001911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCN	ENST00000052754.10	c.324+1090A>G		intron_variant		1	NM_001920.5	ENSP00000052754	P1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57031 AN: 151870 Hom.: 12887 Cov.: 31

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.375

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.376 AC: 57123 AN: 151988 Hom.: 12919 Cov.: 31 AF XY: 0.369 AC XY: 27445 AN XY: 74292

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.375

Alfa AF: 0.300 Hom.: 12207

Bravo AF: 0.405

Asia WGS AF: 0.323 AC: 1125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.83

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: rs516115; hg19: chr12-91557292;