Variant 6-31116271-A-G 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.1344T>C(p.Cys448=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,613,834 control chromosomes in the GnomAD database, including 47,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3212 hom., cov: 31)

Exomes 𝑓: 0.24 ( 44091 hom. )

Consequence

CDSN
NM_001264.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.203

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 6-31116271-A-G is Benign according to our data. Variant chr6-31116271-A-G is described in ClinVar as [Benign]. Clinvar id is 1280864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.203 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 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.1344T>C	p.Cys448=	synonymous_variant	2/2	ENST00000376288.3
PSORS1C1	NM_014068.3 linkuse as main transcript	c.-229+1380A>G		intron_variant		ENST00000259881.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDSN	ENST00000376288.3 linkuse as main transcript	c.1344T>C	p.Cys448=	synonymous_variant	2/2	1	NM_001264.5	P1
PSORS1C1	ENST00000259881.10 linkuse as main transcript	c.-229+1380A>G		intron_variant		1	NM_014068.3	P2	Q9UIG5-1

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30720

AN:

151910

Hom.:

3204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.274

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.0955

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.176

GnomAD3 exomes

AF:

0.183

AC:

45996

AN:

251238

Hom.:

4683

AF XY:

0.187

AC XY:

25323

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.0987

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.170

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.124

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.238

AC:

347980

AN:

1461808

Hom.:

44091

Cov.:

AF XY:

0.236

AC XY:

171652

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.161

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.236

GnomAD4 genome

AF:

0.202

AC:

30754

AN:

152026

Hom.:

3212

Cov.:

AF XY:

0.196

AC XY:

14555

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.167

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.226

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.219

Hom.:

6062

Bravo

AF:

0.202

Asia WGS

AF:

0.169

AC:

587

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	Labcorp Genetics (formerly Invitae), Labcorp	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

-0.64

CADD

Benign

5.2

DANN

Benign

0.76

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