Variant rs1062470 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id is 1643739.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-31116658-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CDSN	NM_001264.5 linkuse as main transcript	c.957C>T	p.Tyr319Tyr	synonymous_variant	2/2	ENST00000376288.3	NP_001255.4	Q15517G8JLG2
PSORS1C1	NM_014068.3 linkuse as main transcript	c.-229+1767G>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.957C>T	p.Tyr319Tyr	synonymous_variant	2/2	1	NM_001264.5	ENSP00000365465.2		G8JLG2
PSORS1C1	ENST00000259881.10 linkuse as main transcript	c.-229+1767G>A		intron_variant		1	NM_014068.3	ENSP00000259881.9		Q9UIG5-1

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

GnomAD3 exomes

AF:

0.366

AC:

89592

AN:

244670

Hom.:

17246

AF XY:

0.358

AC XY:

47770

AN XY:

133448

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 SAS exome

AF:

0.315

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

Gnomad4 AFR exome

AF:

0.565

Gnomad4 AMR exome

AF:

0.397

Gnomad4 ASJ exome

AF:

0.391

Gnomad4 EAS exome

AF:

0.481

Gnomad4 SAS exome

AF:

0.308

Gnomad4 FIN exome

AF:

0.313

Gnomad4 NFE exome

AF:

0.316

Gnomad4 OTH exome

AF:

0.344

GnomAD4 genome

AF:

0.409

AC:

62166

AN:

152038

Hom.:

13543

Cov.:

AF XY:

0.406

AC XY:

30196

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.574

Gnomad4 AMR

AF:

0.410

Gnomad4 ASJ

AF:

0.374

Gnomad4 EAS

AF:

0.517

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.307

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.412

Alfa

AF:

0.342

Hom.:

11837

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.2

DANN

Benign

0.82

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

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