dbSNP rs1062470: CDSN:p.Tyr319Tyr (chr6-31116658-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001264.5(CDSN):c.957C>T(p.Tyr319Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,612,366 control chromosomes in the GnomAD database, including 95,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 13543 hom., cov: 32)

Exomes 𝑓: 0.33 ( 82448 hom. )

Consequence

CDSN
NM_001264.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.15

Publications

60 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 6-31116658-G-A is Benign according to our data. Variant chr6-31116658-G-A is described in ClinVar as Benign. ClinVar VariationId is 1643739.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDSN	NM_001264.5 link	c.957C>T	p.Tyr319Tyr	synonymous_variant	Exon 2 of 2	ENST00000376288.3	NP_001255.4
PSORS1C1	NM_014068.3 link	c.-229+1767G>A		intron_variant	Intron 1 of 5	ENST00000259881.10	NP_054787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDSN	ENST00000376288.3 link	c.957C>T	p.Tyr319Tyr	synonymous_variant	Exon 2 of 2	1	NM_001264.5	ENSP00000365465.2
PSORS1C1	ENST00000259881.10 link	c.-229+1767G>A		intron_variant	Intron 1 of 5	1	NM_014068.3	ENSP00000259881.9

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62101

AN:

151920

Hom.:

13528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.575

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.413

GnomAD2 exomes

AF:

0.366

AC:

89592

AN:

244670

AF XY:

0.358

show subpopulations

Gnomad AFR exome

AF:

0.571

Gnomad AMR exome

AF:

0.397

Gnomad ASJ exome

AF:

0.389

Gnomad EAS exome

AF:

0.513

Gnomad FIN exome

AF:

0.315

Gnomad NFE exome

AF:

0.326

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.331

AC:

482923

AN:

1460328

Hom.:

82448

Cov.:

AF XY:

0.329

AC XY:

239207

AN XY:

726394

show subpopulations

African (AFR)

AF:

0.565

AC:

18907

AN:

33474

American (AMR)

AF:

0.397

AC:

17736

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

10220

AN:

26136

East Asian (EAS)

AF:

0.481

AC:

19113

AN:

39696

South Asian (SAS)

AF:

0.308

AC:

26600

AN:

86258

European-Finnish (FIN)

AF:

0.313

AC:

16307

AN:

52028

Middle Eastern (MID)

AF:

0.430

AC:

2483

AN:

5768

European-Non Finnish (NFE)

AF:

0.316

AC:

350812

AN:

1111876

Other (OTH)

AF:

0.344

AC:

20745

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

23076

46152

69228

92304

115380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11576

23152

34728

46304

57880

<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:

0.409

AC:

62166

AN:

152038

Hom.:

13543

Cov.:

AF XY:

0.406

AC XY:

30196

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.574

AC:

23814

AN:

41456

American (AMR)

AF:

0.410

AC:

6270

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1297

AN:

3472

East Asian (EAS)

AF:

0.517

AC:

2663

AN:

5152

South Asian (SAS)

AF:

0.288

AC:

1389

AN:

4824

European-Finnish (FIN)

AF:

0.307

AC:

3249

AN:

10590

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.327

AC:

22212

AN:

67956

Other (OTH)

AF:

0.412

AC:

867

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1831

3662

5492

7323

9154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.354

Hom.:

31463

Bravo

AF:

0.428

Asia WGS

AF:

0.354

AC:

1230

AN:

3478

EpiCase

AF:

0.325

EpiControl

AF:

0.327

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.2

(source)

DANN

Benign

0.82

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over