dbSNP rs3094212: CDSN:c.86-464C>T (chr6-31117993-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001264.5(CDSN):c.86-464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 172,064 control chromosomes in the GnomAD database, including 29,182 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 26168 hom., cov: 31)

Exomes 𝑓: 0.52 ( 3014 hom. )

Consequence

CDSN
NM_001264.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00500

Publications

43 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDSN	NM_001264.5 link	c.86-464C>T		intron_variant	Intron 1 of 1	ENST00000376288.3	NP_001255.4	Q15517G8JLG2
PSORS1C1	NM_014068.3 link	c.-229+3102G>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	ENST00000376288.3 link	c.86-464C>T		intron_variant	Intron 1 of 1	1	NM_001264.5	ENSP00000365465.2		G8JLG2
PSORS1C1	ENST00000259881.10 link	c.-229+3102G>A		intron_variant	Intron 1 of 5	1	NM_014068.3	ENSP00000259881.9		Q9UIG5-1

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88064

AN:

151804

Hom.:

26152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.682

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.617

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.718

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.688

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.600

GnomAD4 exome

AF:

0.518

AC:

10442

AN:

20142

Hom.:

3014

Cov.:

AF XY:

0.523

AC XY:

5600

AN XY:

10716

show subpopulations

African (AFR)

AF:

0.599

AC:

151

AN:

252

American (AMR)

AF:

0.588

AC:

1701

AN:

2892

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

188

AN:

308

East Asian (EAS)

AF:

0.673

AC:

793

AN:

1178

South Asian (SAS)

AF:

0.631

AC:

1708

AN:

2706

European-Finnish (FIN)

AF:

0.408

AC:

159

AN:

390

Middle Eastern (MID)

AF:

0.519

AC:

AN:

European-Non Finnish (NFE)

AF:

0.460

AC:

5285

AN:

11480

Other (OTH)

AF:

0.486

AC:

429

AN:

882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

213

426

639

852

1065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

248

372

496

620

<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:

0.580

AC:

88122

AN:

151922

Hom.:

26168

Cov.:

AF XY:

0.584

AC XY:

43338

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.682

AC:

28250

AN:

41410

American (AMR)

AF:

0.617

AC:

9405

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.671

AC:

2328

AN:

3468

East Asian (EAS)

AF:

0.718

AC:

3703

AN:

5160

South Asian (SAS)

AF:

0.618

AC:

2975

AN:

4814

European-Finnish (FIN)

AF:

0.504

AC:

5308

AN:

10542

Middle Eastern (MID)

AF:

0.688

AC:

201

AN:

292

European-Non Finnish (NFE)

AF:

0.505

AC:

34334

AN:

67966

Other (OTH)

AF:

0.599

AC:

1264

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1861

3722

5584

7445

9306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.542

Hom.:

93432

Bravo

AF:

0.594

Asia WGS

AF:

0.640

AC:

2227

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.0

(source)

DANN

Benign

0.78

PhyloP100

-0.0050

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over