Variant rs4713436 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001264.5(CDSN):c.753G>A(p.Arg251=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,613,678 control chromosomes in the GnomAD database, including 27,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2457 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25498 hom. )

Consequence

CDSN
NM_001264.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.577

Variant links:

Genes affected

CDSN (HGNC:1802): (corneodesmosin) This gene encodes a protein found in corneodesmosomes, which localize to human epidermis and other cornified squamous epithelia. The encoded protein undergoes a series of cleavages during corneocyte maturation. This gene is highly polymorphic in human populations, and variation has been associated with skin diseases such as psoriasis, hypotrichosis and peeling skin syndrome. The gene is located in the major histocompatibility complex (MHC) class I region on chromosome 6. [provided by RefSeq, Dec 2014]

CDSN links:

PSORS1C1 (HGNC:17202): (psoriasis susceptibility 1 candidate 1) This gene is one of several genes thought to confer susceptibility to psoriasis and systemic sclerosis, located on chromosome 6 near the major histocompatibility complex (MHC) class I region. [provided by RefSeq, Sep 2011]

PSORS1C1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 6-31116862-C-T is Benign according to our data. Variant chr6-31116862-C-T is described in ClinVar as [Benign]. Clinvar id is 1237033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.577 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDSN	NM_001264.5 linkuse as main transcript	c.753G>A	p.Arg251=	synonymous_variant	2/2	ENST00000376288.3
PSORS1C1	NM_014068.3 linkuse as main transcript	c.-229+1971C>T		intron_variant		ENST00000259881.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDSN	ENST00000376288.3 linkuse as main transcript	c.753G>A	p.Arg251=	synonymous_variant	2/2	1	NM_001264.5	P1
PSORS1C1	ENST00000259881.10 linkuse as main transcript	c.-229+1971C>T		intron_variant		1	NM_014068.3	P2	Q9UIG5-1

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25956

AN:

152010

Hom.:

2461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.188

GnomAD3 exomes

AF:

0.208

AC:

51547

AN:

248348

Hom.:

5865

AF XY:

0.216

AC XY:

29154

AN XY:

134782

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.211

Gnomad SAS exome

AF:

0.325

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.190

Gnomad OTH exome

AF:

0.217

GnomAD4 exome

AF:

0.179

AC:

260910

AN:

1461550

Hom.:

25498

Cov.:

AF XY:

0.185

AC XY:

134589

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.199

Gnomad4 SAS exome

AF:

0.327

Gnomad4 FIN exome

AF:

0.196

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.182

GnomAD4 genome

AF:

0.171

AC:

25949

AN:

152128

Hom.:

2457

Cov.:

AF XY:

0.177

AC XY:

13133

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.329

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.178

Gnomad4 OTH

AF:

0.187

Alfa

AF:

0.177

Hom.:

1797

Bravo

AF:

0.165

Asia WGS

AF:

0.286

AC:

996

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over