rs7441

Variant names:

• chr12-91145898-G-A
• rs7441
• ENST00000393155.6:n.*893C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001920.5(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 NM_001920.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.52
• Publications: 22 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 -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.
• 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 rank	MANE	Protein	UniProt
DCN	NM_001920.5	c.*160C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000052754.10	NP_001911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCN	ENST00000052754.10	c.*160C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_001920.5	ENSP00000052754.5

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

African (AFR) AF: 0.170 AC: 2169 AN: 12778

American (AMR) AF: 0.0565 AC: 1097 AN: 19400

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 2036 AN: 14330

East Asian (EAS) AF: 0.0575 AC: 1777 AN: 30910

South Asian (SAS) AF: 0.0441 AC: 1986 AN: 45054

European-Finnish (FIN) AF: 0.0460 AC: 1426 AN: 30994

Middle Eastern (MID) AF: 0.110 AC: 308 AN: 2804

European-Non Finnish (NFE) AF: 0.0699 AC: 20589 AN: 294516

Other (OTH) AF: 0.0790 AC: 2134 AN: 27026

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

African (AFR) AF: 0.174 AC: 7206 AN: 41518

American (AMR) AF: 0.0744 AC: 1137 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 507 AN: 3472

East Asian (EAS) AF: 0.0550 AC: 285 AN: 5182

South Asian (SAS) AF: 0.0405 AC: 195 AN: 4818

European-Finnish (FIN) AF: 0.0439 AC: 465 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0680 AC: 4624 AN: 68010

Other (OTH) AF: 0.100 AC: 211 AN: 2110

Alfa AF: 0.0790 Hom.: 1178

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital stromal corneal dystrophy Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		2.5
PromoterAI		0.0038	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: rs7441; hg19: chr12-91539675;