rs7742033

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.166C>T(p.Leu56Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,557,208 control chromosomes in the GnomAD database, including 341 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.022 ( 71 hom., cov: 33)

Exomes 𝑓: 0.012 ( 270 hom. )

Consequence

CDSN
NM_001264.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00900

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=0.00291425).

BP6

Variant 6-31117449-G-A is Benign according to our data. Variant chr6-31117449-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1321061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDSN	NM_001264.5 link	c.166C>T	p.Leu56Phe	missense_variant	Exon 2 of 2	ENST00000376288.3	NP_001255.4	Q15517G8JLG2
PSORS1C1	NM_014068.3 link	c.-229+2558G>A		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.166C>T	p.Leu56Phe	missense_variant	Exon 2 of 2	1	NM_001264.5	ENSP00000365465.2		G8JLG2
PSORS1C1	ENST00000259881.10 link	c.-229+2558G>A		intron_variant	Intron 1 of 5	1	NM_014068.3	ENSP00000259881.9		Q9UIG5-1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3318

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0173

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.00970

Gnomad OTH

AF:

0.0336

GnomAD2 exomes

AF:

0.0160

AC:

2574

AN:

160586

AF XY:

0.0166

show subpopulations

Gnomad AFR exome

AF:

0.0467

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.0541

Gnomad EAS exome

AF:

0.000753

Gnomad FIN exome

AF:

0.000633

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0260

GnomAD4 exome

AF:

0.0121

AC:

17019

AN:

1404910

Hom.:

270

Cov.:

AF XY:

0.0126

AC XY:

8717

AN XY:

693598

show subpopulations

Gnomad4 AFR exome

AF:

0.0470

AC:

1504

AN:

31978

Gnomad4 AMR exome

AF:

0.0147

AC:

535

AN:

36324

Gnomad4 ASJ exome

AF:

0.0527

AC:

1328

AN:

25218

Gnomad4 EAS exome

AF:

0.000687

AC:

AN:

36380

Gnomad4 SAS exome

AF:

0.0244

AC:

1946

AN:

79662

Gnomad4 FIN exome

AF:

0.000882

AC:

AN:

48740

Gnomad4 NFE exome

AF:

0.00924

AC:

9999

AN:

1082588

Gnomad4 Remaining exome

AF:

0.0192

AC:

1117

AN:

58320

Heterozygous variant carriers

979

1958

2937

3916

4895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.0218

AC:

3318

AN:

152298

Hom.:

Cov.:

AF XY:

0.0217

AC XY:

1614

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0488

AC:

0.048811

AN:

0.048811

Gnomad4 AMR

AF:

0.0172

AC:

0.017185

AN:

0.017185

Gnomad4 ASJ

AF:

0.0490

AC:

0.0489631

AN:

0.0489631

Gnomad4 EAS

AF:

0.00174

AC:

0.00173812

AN:

0.00173812

Gnomad4 SAS

AF:

0.0186

AC:

0.0186335

AN:

0.0186335

Gnomad4 FIN

AF:

0.000565

AC:

0.000565078

AN:

0.000565078

Gnomad4 NFE

AF:

0.00970

AC:

0.00970103

AN:

0.00970103

Gnomad4 OTH

AF:

0.0327

AC:

0.0327324

AN:

0.0327324

Heterozygous variant carriers

163

326

490

653

816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0155

Hom.:

148

Bravo

AF:

0.0247

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.0378

AC:

134

ESP6500EA

AF:

0.00788

AC:

ExAC

AF:

0.0102

AC:

1129

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 17, 2023

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.027

Sift

Benign

0.060

Sift4G

Benign

0.087

Vest4

0.13

MPC

0.34

ClinPred

0.0059

GERP RS

2.0

gMVP

0.38

Mutation Taster

=100/0

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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