6-31116090-G-A

Position:

chr6-31116090-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001264.5(CDSN):c.1525C>T(p.Leu509Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,612,108 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

CDSN
NM_001264.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.76

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:

PSORS1C1 (HGNC:):

PSORS1C1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 6-31116090-G-A is Benign according to our data. Variant chr6-31116090-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 716000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-31116090-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.76 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00214 (326/152318) while in subpopulation NFE AF= 0.00228 (155/68028). AF 95% confidence interval is 0.00199. There are 2 homozygotes in gnomad4. There are 194 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDSN	NM_001264.5 linkuse as main transcript	c.1525C>T	p.Leu509Leu	synonymous_variant	2/2	ENST00000376288.3	NP_001255.4	Q15517G8JLG2
PSORS1C1	NM_014068.3 linkuse as main transcript	c.-229+1199G>A		intron_variant		ENST00000259881.10	NP_054787.2	Q9UIG5-1D2IYL0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDSN	ENST00000376288.3 linkuse as main transcript	c.1525C>T	p.Leu509Leu	synonymous_variant	2/2	1	NM_001264.5	ENSP00000365465.2		G8JLG2
PSORS1C1	ENST00000259881.10 linkuse as main transcript	c.-229+1199G>A		intron_variant		1	NM_014068.3	ENSP00000259881.9		Q9UIG5-1

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

326

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00207

AC:

510

AN:

246322

Hom.:

AF XY:

0.00198

AC XY:

266

AN XY:

134198

show subpopulations

Gnomad AFR exome

AF:

0.000396

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00142

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000363

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.00206

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.00165

AC:

2414

AN:

1459790

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1206

AN XY:

726096

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.000767

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000395

Gnomad4 FIN exome

AF:

0.00916

Gnomad4 NFE exome

AF:

0.00160

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00214

AC:

326

AN:

152318

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

194

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0129

Gnomad4 NFE

AF:

0.00228

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00206

Hom.:

Bravo

AF:

0.00116

EpiCase

AF:

0.00229

EpiControl

AF:

0.00213

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	CDSN: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 21, 2023	- -

Hypotrichosis 2;C1849193:Peeling skin syndrome 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.3

DANN

Benign

0.88

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