chr12-91181430-T-A

Variant names:

• chr12-91181430-T-A
• rs13312816
• NM_001920.5:c.-34+1225A>T

Variant summary

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

The NM_001920.5(DCN):​c.-34+1225A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 151,992 control chromosomes in the GnomAD database, including 1,734 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 (1734 hom., cov: 32)
• Consequence: DCN NM_001920.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 6 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

ENSG00000293802 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCN	NM_001920.5	c.-34+1225A>T		intron_variant	Intron 1 of 7	ENST00000052754.10	NP_001911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCN	ENST00000052754.10	c.-34+1225A>T		intron_variant	Intron 1 of 7	1	NM_001920.5	ENSP00000052754.5

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19046 AN: 151874 Hom.: 1724 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0666

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0687

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.126 AC: 19088 AN: 151992 Hom.: 1734 Cov.: 32 AF XY: 0.123 AC XY: 9121 AN XY: 74322

African (AFR) AF: 0.251 AC: 10391 AN: 41426

American (AMR) AF: 0.108 AC: 1639 AN: 15228

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

East Asian (EAS) AF: 0.139 AC: 718 AN: 5162

South Asian (SAS) AF: 0.0666 AC: 322 AN: 4834

European-Finnish (FIN) AF: 0.0441 AC: 468 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0687 AC: 4668 AN: 67942

Other (OTH) AF: 0.125 AC: 265 AN: 2112

Alfa AF: 0.0970 Hom.: 173

Bravo AF: 0.138

Asia WGS AF: 0.108 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.0
DANN	Benign	0.81
PhyloP100		1.7
PromoterAI		-0.0052	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: rs13312816; hg19: chr12-91575207;