Genetic Variant CDSN:p.Leu410Ser (chr6-31116386-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001264.5(CDSN):c.1229T>C(p.Leu410Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,603,348 control chromosomes in the GnomAD database, including 217,911 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.58 ( 26123 hom., cov: 31)

Exomes 𝑓: 0.51 ( 191788 hom. )

Consequence

CDSN
NM_001264.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.368

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.5814186E-6).

BP6

Variant 6-31116386-A-G is Benign according to our data. Variant chr6-31116386-A-G is described in ClinVar as [Benign]. Clinvar id is 1600234.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-31116386-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDSN	NM_001264.5 link	c.1229T>C	p.Leu410Ser	missense_variant	Exon 2 of 2	ENST00000376288.3	NP_001255.4	Q15517G8JLG2
PSORS1C1	NM_014068.3 link	c.-229+1495A>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.1229T>C	p.Leu410Ser	missense_variant	Exon 2 of 2	1	NM_001264.5	ENSP00000365465.2		G8JLG2
PSORS1C1	ENST00000259881.10 link	c.-229+1495A>G		intron_variant	Intron 1 of 5	1	NM_014068.3	ENSP00000259881.9		Q9UIG5-1

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

87962

AN:

151652

Hom.:

26108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.682

Gnomad AMI

AF:

0.387

Gnomad AMR

AF:

0.617

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.718

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.600

GnomAD3 exomes

AF:

0.571

AC:

132540

AN:

232242

Hom.:

38416

AF XY:

0.571

AC XY:

71596

AN XY:

125400

show subpopulations

Gnomad AFR exome

AF:

0.677

Gnomad AMR exome

AF:

0.586

Gnomad ASJ exome

AF:

0.658

Gnomad EAS exome

AF:

0.720

Gnomad SAS exome

AF:

0.639

Gnomad FIN exome

AF:

0.509

Gnomad NFE exome

AF:

0.510

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.508

AC:

738095

AN:

1451580

Hom.:

191788

Cov.:

AF XY:

0.514

AC XY:

370440

AN XY:

721312

show subpopulations

Gnomad4 AFR exome

AF:

0.676

Gnomad4 AMR exome

AF:

0.589

Gnomad4 ASJ exome

AF:

0.658

Gnomad4 EAS exome

AF:

0.680

Gnomad4 SAS exome

AF:

0.635

Gnomad4 FIN exome

AF:

0.508

Gnomad4 NFE exome

AF:

0.479

Gnomad4 OTH exome

AF:

0.525

GnomAD4 genome

AF:

0.580

AC:

88018

AN:

151768

Hom.:

26123

Cov.:

AF XY:

0.584

AC XY:

43273

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.682

Gnomad4 AMR

AF:

0.616

Gnomad4 ASJ

AF:

0.671

Gnomad4 EAS

AF:

0.718

Gnomad4 SAS

AF:

0.617

Gnomad4 FIN

AF:

0.504

Gnomad4 NFE

AF:

0.505

Gnomad4 OTH

AF:

0.599

Alfa

AF:

0.537

Hom.:

14072

Bravo

AF:

0.594

TwinsUK

AF:

0.475

AC:

1761

ALSPAC

AF:

0.455

AC:

1753

ESP6500AA

AF:

0.662

AC:

2918

ESP6500EA

AF:

0.508

AC:

4371

ExAC

AF:

0.561

AC:

67864

Asia WGS

AF:

0.640

AC:

2227

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.3

DANN

Benign

0.68

DEOGEN2

Benign

0.0020

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.00076

LIST_S2

Benign

0.17

MetaRNN

Benign

0.0000046

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.33

PROVEAN

Benign

1.4

REVEL

Benign

0.029

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.025

MPC

0.43

ClinPred

0.0070

GERP RS

1.4

gMVP

0.042

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

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