rs3138241

Variant names:

• chr12-91159244-C-T
• rs3138241
• NM_001920.5:c.325-735G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001920.5(DCN):​c.325-735G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 151,994 control chromosomes in the GnomAD database, including 951 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 0.097 (951 hom., cov: 32)
• Consequence: DCN NM_001920.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 3 publications found

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]

DCN Gene-Disease associations (from GenCC):

• congenital stromal corneal dystrophy

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

ACMG classification

Our verdict: Benign. The variant received -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 = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCN	NM_001920.5	c.325-735G>A		intron_variant	Intron 3 of 7	ENST00000052754.10	NP_001911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCN	ENST00000052754.10	c.325-735G>A		intron_variant	Intron 3 of 7	1	NM_001920.5	ENSP00000052754.5

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14721 AN: 151874 Hom.: 949 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0745

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.0411

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0684

Gnomad OTH AF: 0.0962

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

GnomAD4 genome AF: 0.0970 AC: 14743 AN: 151994 Hom.: 951 Cov.: 32 AF XY: 0.0939 AC XY: 6978 AN XY: 74304

African (AFR) AF: 0.174 AC: 7214 AN: 41440

American (AMR) AF: 0.0744 AC: 1136 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 507 AN: 3468

East Asian (EAS) AF: 0.0548 AC: 283 AN: 5162

South Asian (SAS) AF: 0.0407 AC: 196 AN: 4814

European-Finnish (FIN) AF: 0.0439 AC: 463 AN: 10552

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0684 AC: 4651 AN: 67976

Other (OTH) AF: 0.0999 AC: 211 AN: 2112

Alfa AF: 0.0906 Hom.: 122

Bravo AF: 0.103

Asia WGS AF: 0.0550 AC: 194 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3138241; hg19: chr12-91553021;