Genetic Variant CDSN:c.*146C>T (chr6-31115879-G-A) – 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.*146C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 676,110 control chromosomes in the GnomAD database, including 101,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.58 ( 26021 hom., cov: 30)

Exomes 𝑓: 0.53 ( 75374 hom. )

Consequence

CDSN
NM_001264.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.147

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 6-31115879-G-A is Benign according to our data. Variant chr6-31115879-G-A is described in ClinVar as [Benign]. Clinvar id is 1266446.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDSN	NM_001264.5 link	c.*146C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000376288.3	NP_001255.4	Q15517G8JLG2
PSORS1C1	NM_014068.3 link	c.-229+988G>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 link	c.*146C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_001264.5	ENSP00000365465.2		G8JLG2
PSORS1C1	ENST00000259881.10 link	c.-229+988G>A		intron_variant	Intron 1 of 5	1	NM_014068.3	ENSP00000259881.9		Q9UIG5-1

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

87787

AN:

151560

Hom.:

26005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.682

Gnomad AMI

AF:

0.387

Gnomad AMR

AF:

0.617

Gnomad ASJ

AF:

0.670

Gnomad EAS

AF:

0.716

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.688

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.599

GnomAD4 exome

AF:

0.527

AC:

276277

AN:

524432

Hom.:

75374

Cov.:

AF XY:

0.531

AC XY:

146184

AN XY:

275154

show subpopulations

Gnomad4 AFR exome

AF:

0.660

Gnomad4 AMR exome

AF:

0.556

Gnomad4 ASJ exome

AF:

0.630

Gnomad4 EAS exome

AF:

0.674

Gnomad4 SAS exome

AF:

0.611

Gnomad4 FIN exome

AF:

0.498

Gnomad4 NFE exome

AF:

0.487

Gnomad4 OTH exome

AF:

0.535

GnomAD4 genome

AF:

0.579

AC:

87845

AN:

151678

Hom.:

26021

Cov.:

AF XY:

0.582

AC XY:

43167

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.682

Gnomad4 AMR

AF:

0.616

Gnomad4 ASJ

AF:

0.670

Gnomad4 EAS

AF:

0.715

Gnomad4 SAS

AF:

0.617

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.505

Gnomad4 OTH

AF:

0.598

Alfa

AF:

0.536

Hom.:

31800

Bravo

AF:

0.594

Asia WGS

AF:

0.640

AC:

2226

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.4

DANN

Benign

0.51

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