chr6-31117449-G-A

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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

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

Publications

15 publications found

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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001264.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDSN	NM_001264.5	MANE Select	c.166C>T	p.Leu56Phe	missense	Exon 2 of 2	NP_001255.4
	PSORS1C1	NM_014068.3	MANE Select	c.-229+2558G>A		intron	N/A	NP_054787.2	Q9UIG5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDSN	ENST00000376288.3	TSL:1 MANE Select	c.166C>T	p.Leu56Phe	missense	Exon 2 of 2	ENSP00000365465.2	Q15517
PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.-229+2558G>A		intron	N/A	ENSP00000259881.9	Q9UIG5-1
PSORS1C1	ENST00000479581.5	TSL:1	n.61+2558G>A		intron	N/A

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

African (AFR)

AF:

0.0470

AC:

1504

AN:

31978

American (AMR)

AF:

0.0147

AC:

535

AN:

36324

Ashkenazi Jewish (ASJ)

AF:

0.0527

AC:

1328

AN:

25218

East Asian (EAS)

AF:

0.000687

AC:

AN:

36380

South Asian (SAS)

AF:

0.0244

AC:

1946

AN:

79662

European-Finnish (FIN)

AF:

0.000882

AC:

AN:

48740

Middle Eastern (MID)

AF:

0.0916

AC:

522

AN:

5700

European-Non Finnish (NFE)

AF:

0.00924

AC:

9999

AN:

1082588

Other (OTH)

AF:

0.0192

AC:

1117

AN:

58320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

979

1958

2937

3916

4895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

African (AFR)

AF:

0.0488

AC:

2028

AN:

41548

American (AMR)

AF:

0.0172

AC:

263

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0490

AC:

170

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5178

South Asian (SAS)

AF:

0.0186

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00970

AC:

660

AN:

68034

Other (OTH)

AF:

0.0327

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

163

326

490

653

816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

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

PhyloP100

-0.0090

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over