12-91178638-C-T

Variant names:

• chr12-91178638-C-T
• rs3138167
• NM_001920.5:c.-33-53G>A

Variant summary

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

The NM_133504.3(DCN):​c.-86G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 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_133504.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133504.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCN	NM_001920.5	MANE Select	c.-33-53G>A		intron	N/A	NP_001911.1
	DCN	NM_133504.3		c.-86G>A		5_prime_UTR	Exon 1 of 5	NP_598011.1
	DCN	NM_133505.3		c.-86G>A		5_prime_UTR	Exon 1 of 4	NP_598012.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCN	ENST00000052754.10	TSL:1 MANE Select	c.-33-53G>A		intron	N/A	ENSP00000052754.5
	DCN	ENST00000393155.6	TSL:1	n.-33-53G>A		intron	N/A	ENSP00000376862.2
	DCN	ENST00000880707.1		c.-86G>A		5_prime_UTR	Exon 1 of 7	ENSP00000550766.1

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

African (AFR) AF: 0.278 AC: 6433 AN: 23112

American (AMR) AF: 0.125 AC: 5166 AN: 41182

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 3507 AN: 22586

East Asian (EAS) AF: 0.152 AC: 5596 AN: 36752

South Asian (SAS) AF: 0.0656 AC: 4865 AN: 74214

European-Finnish (FIN) AF: 0.0456 AC: 2374 AN: 52038

Middle Eastern (MID) AF: 0.126 AC: 601 AN: 4752

European-Non Finnish (NFE) AF: 0.0673 AC: 43367 AN: 643918

Other (OTH) AF: 0.0934 AC: 4043 AN: 43278

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

African (AFR) AF: 0.277 AC: 11474 AN: 41354

American (AMR) AF: 0.113 AC: 1719 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3470

East Asian (EAS) AF: 0.139 AC: 714 AN: 5150

South Asian (SAS) AF: 0.0673 AC: 324 AN: 4812

European-Finnish (FIN) AF: 0.0439 AC: 463 AN: 10544

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0691 AC: 4700 AN: 67976

Other (OTH) AF: 0.133 AC: 280 AN: 2110

Alfa AF: 0.0992 Hom.: 1363

Bravo AF: 0.147

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.21
DANN	Benign	0.45
PhyloP100		-0.75
PromoterAI		-0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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