6-31116168-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001264.5(CDSN):c.1447G>A(p.Ala483Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00605 in 1,611,710 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0061 ( 67 hom. )

Consequence

CDSN
NM_001264.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.21

Publications

8 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=0.007544428).

BP6

Variant 6-31116168-C-T is Benign according to our data. Variant chr6-31116168-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 391650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00545 (829/152222) while in subpopulation NFE AF = 0.00943 (641/68008). AF 95% confidence interval is 0.00882. There are 6 homozygotes in GnomAd4. There are 368 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AD,AR gene

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.1447G>A	p.Ala483Thr	missense	Exon 2 of 2	NP_001255.4
	PSORS1C1	NM_014068.3	MANE Select	c.-229+1277C>T		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.1447G>A	p.Ala483Thr	missense	Exon 2 of 2	ENSP00000365465.2	Q15517
PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.-229+1277C>T		intron	N/A	ENSP00000259881.9	Q9UIG5-1
PSORS1C1	ENST00000479581.5	TSL:1	n.61+1277C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00545

AC:

829

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00655

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00942

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00600

AC:

1482

AN:

246928

AF XY:

0.00652

show subpopulations

Gnomad AFR exome

AF:

0.000456

Gnomad AMR exome

AF:

0.00374

Gnomad ASJ exome

AF:

0.00305

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.00223

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00908

GnomAD4 exome

AF:

0.00611

AC:

8920

AN:

1459488

Hom.:

Cov.:

AF XY:

0.00635

AC XY:

4609

AN XY:

725736

show subpopulations

African (AFR)

AF:

0.000778

AC:

AN:

33432

American (AMR)

AF:

0.00401

AC:

179

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.00377

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.000824

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.00172

AC:

AN:

52890

Middle Eastern (MID)

AF:

0.00573

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00730

AC:

8111

AN:

1110568

Other (OTH)

AF:

0.00516

AC:

311

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

539

1078

1616

2155

2694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

216

432

648

864

1080

<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:

0.00545

AC:

829

AN:

152222

Hom.:

Cov.:

AF XY:

0.00494

AC XY:

368

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

41536

American (AMR)

AF:

0.00654

AC:

100

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000943

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00943

AC:

641

AN:

68008

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

124

166

207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00667

Hom.:

Bravo

AF:

0.00547

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000720

AC:

ESP6500EA

AF:

0.00735

AC:

ExAC

AF:

0.00639

AC:

770

Asia WGS

AF:

0.00144

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)

CDSN-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0075

MetaSVM

Benign

-1.1

PhyloP100

2.2

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.082

Sift

Uncertain

0.0070

Sift4G

Benign

0.11

Vest4

0.38

MVP

0.41

MPC

0.95

ClinPred

0.020

GERP RS

4.1

gMVP

0.22

Mutation Taster

=96/4

polymorphism

(source)

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

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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