rs707913

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001264.5(CDSN):c.605T>C(p.Phe202Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,613,866 control chromosomes in the GnomAD database, including 41,221 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5986 hom., cov: 33)

Exomes 𝑓: 0.21 ( 35235 hom. )

Consequence

CDSN
NM_001264.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.71

Publications

30 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037157536).

BP6

Variant 6-31117010-A-G is Benign according to our data. Variant chr6-31117010-A-G is described in ClinVar as Benign. ClinVar VariationId is 1231588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDSN	NM_001264.5 link	c.605T>C	p.Phe202Ser	missense_variant	Exon 2 of 2	ENST00000376288.3	NP_001255.4	Q15517G8JLG2
PSORS1C1	NM_014068.3 link	c.-229+2119A>G		intron_variant	Intron 1 of 5	ENST00000259881.10	NP_054787.2	Q9UIG5-1D2IYL0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDSN	ENST00000376288.3 link	c.605T>C	p.Phe202Ser	missense_variant	Exon 2 of 2	1	NM_001264.5	ENSP00000365465.2		G8JLG2
PSORS1C1	ENST00000259881.10 link	c.-229+2119A>G		intron_variant	Intron 1 of 5	1	NM_014068.3	ENSP00000259881.9		Q9UIG5-1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40984

AN:

151934

Hom.:

5979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.0872

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.265

GnomAD2 exomes

AF:

0.233

AC:

58514

AN:

251430

AF XY:

0.218

show subpopulations

Gnomad AFR exome

AF:

0.380

Gnomad AMR exome

AF:

0.325

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.216

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.212

AC:

310124

AN:

1461816

Hom.:

35235

Cov.:

AF XY:

0.207

AC XY:

150335

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.380

AC:

12738

AN:

33478

American (AMR)

AF:

0.322

AC:

14387

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

5520

AN:

26136

East Asian (EAS)

AF:

0.321

AC:

12741

AN:

39700

South Asian (SAS)

AF:

0.0778

AC:

6708

AN:

86258

European-Finnish (FIN)

AF:

0.207

AC:

11056

AN:

53420

Middle Eastern (MID)

AF:

0.167

AC:

963

AN:

5768

European-Non Finnish (NFE)

AF:

0.210

AC:

233356

AN:

1111946

Other (OTH)

AF:

0.210

AC:

12655

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

16379

32757

49136

65514

81893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8122

16244

24366

32488

40610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.270

AC:

41023

AN:

152050

Hom.:

5986

Cov.:

AF XY:

0.266

AC XY:

19790

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.379

AC:

15737

AN:

41480

American (AMR)

AF:

0.316

AC:

4835

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

726

AN:

3472

East Asian (EAS)

AF:

0.338

AC:

1739

AN:

5150

South Asian (SAS)

AF:

0.0873

AC:

421

AN:

4822

European-Finnish (FIN)

AF:

0.202

AC:

2143

AN:

10586

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14708

AN:

67944

Other (OTH)

AF:

0.267

AC:

563

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1545

3089

4634

6178

7723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.234

Hom.:

11201

Bravo

AF:

0.287

TwinsUK

AF:

0.226

AC:

838

ALSPAC

AF:

0.217

AC:

838

ESP6500AA

AF:

0.358

AC:

1578

ESP6500EA

AF:

0.218

AC:

1876

ExAC

AF:

0.231

AC:

28099

Asia WGS

AF:

0.202

AC:

701

AN:

3478

EpiCase

AF:

0.203

EpiControl

AF:

0.208

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 21307873) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.0026

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.00025

LIST_S2

Benign

0.22

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.91

PhyloP100

1.7

PrimateAI

Benign

0.38

PROVEAN

Benign

3.0

REVEL

Benign

0.044

Sift

Benign

0.55

Sift4G

Benign

1.0

Vest4

0.020

MPC

0.56

ClinPred

0.00088

GERP RS

1.4

gMVP

0.064

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over