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 ENST00000393155.6(DCN):​n.*893C>T variant causes a non coding transcript exon 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 ENST00000393155.6 non_coding_transcript_exon
• 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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393155.6. 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.*160C>T		3_prime_UTR	Exon 8 of 8	NP_001911.1
	DCN	NM_133503.4		c.*160C>T		3_prime_UTR	Exon 8 of 8	NP_598010.1
	DCN	NM_133504.3		c.*160C>T		3_prime_UTR	Exon 5 of 5	NP_598011.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCN	ENST00000393155.6	TSL:1	n.*893C>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000376862.2
	DCN	ENST00000052754.10	TSL:1 MANE Select	c.*160C>T		3_prime_UTR	Exon 8 of 8	ENSP00000052754.5
	DCN	ENST00000425043.5	TSL:1	c.*160C>T		3_prime_UTR	Exon 4 of 4	ENSP00000401021.1

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital stromal corneal dystrophy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;