rs7441

Positions:

• chr12-91145898-G-A
• chr12-91145898-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000052754.10(DCN):​c.*160C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0766 in 630,010 control chromosomes in the GnomAD database, including 2,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (945 hom., cov: 32)
  • Exomes 𝑓: 0.070 (1349 hom.)
• Consequence: DCN ENST00000052754.10 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.52

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 12-91145898-G-A is Benign according to our data. Variant chr12-91145898-G-A is described in ClinVar as [Benign]. Clinvar id is 310647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-91145898-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCN	NM_001920.5	c.*160C>T		3_prime_UTR_variant	8/8	ENST00000052754.10	NP_001911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCN	ENST00000052754.10	c.*160C>T		3_prime_UTR_variant	8/8	1	NM_001920.5	ENSP00000052754	P1

Frequencies

GnomAD3 genomes AF: 0.0966 AC: 14689 AN: 152080 Hom.: 943 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.0745

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0551

Gnomad SAS AF: 0.0409

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0680

Gnomad OTH AF: 0.0963

GnomAD4 exome AF: 0.0702 AC: 33522 AN: 477812 Hom.: 1349 Cov.: 5 AF XY: 0.0687 AC XY: 17495 AN XY: 254694

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.0565

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.0575

Gnomad4 SAS exome AF: 0.0441

Gnomad4 FIN exome AF: 0.0460

Gnomad4 NFE exome AF: 0.0699

Gnomad4 OTH exome AF: 0.0790

GnomAD4 genome AF: 0.0967 AC: 14711 AN: 152198 Hom.: 945 Cov.: 32 AF XY: 0.0935 AC XY: 6959 AN XY: 74408

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.0744

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.0550

Gnomad4 SAS AF: 0.0405

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0680

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0696 Hom.: 329

Bravo AF: 0.103

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Congenital stromal corneal dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.86

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: rs7441; hg19: chr12-91539675;