rs707913

Positions:

• chr6-31117010-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000376288.3(CDSN):​c.605T>C​(p.Phe202Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,613,866 control chromosomes in the GnomAD database, including 41,221 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5986 hom., cov: 33)
  • Exomes 𝑓: 0.21 (35235 hom.)
• Consequence: CDSN ENST00000376288.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.71

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037157536).
• BP6: Variant 6-31117010-A-G is Benign according to our data. Variant chr6-31117010-A-G is described in ClinVar as [Benign]. Clinvar id is 1231588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-31117010-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDSN	NM_001264.5	c.605T>C	p.Phe202Ser	missense_variant	2/2	ENST00000376288.3	NP_001255.4
PSORS1C1	NM_014068.3	c.-229+2119A>G		intron_variant		ENST00000259881.10	NP_054787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDSN	ENST00000376288.3	c.605T>C	p.Phe202Ser	missense_variant	2/2	1	NM_001264.5	ENSP00000365465	P1
PSORS1C1	ENST00000259881.10	c.-229+2119A>G		intron_variant		1	NM_014068.3	ENSP00000259881	P2

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40984 AN: 151934 Hom.: 5979 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.265

GnomAD3 exomes AF: 0.233 AC: 58514 AN: 251430 Hom.: 7680 AF XY: 0.218 AC XY: 29645 AN XY: 135882

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.325

Gnomad ASJ exome AF: 0.212

Gnomad EAS exome AF: 0.324

Gnomad SAS exome AF: 0.0782

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.216

Gnomad OTH exome AF: 0.238

GnomAD4 exome AF: 0.212 AC: 310124 AN: 1461816 Hom.: 35235 Cov.: 75 AF XY: 0.207 AC XY: 150335 AN XY: 727216

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.0778

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.270 AC: 41023 AN: 152050 Hom.: 5986 Cov.: 33 AF XY: 0.266 AC XY: 19790 AN XY: 74328

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.0873

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.267

Alfa AF: 0.225 Hom.: 6714

Bravo AF: 0.287

TwinsUK AF: 0.226 AC: 838

ALSPAC AF: 0.217 AC: 838

ESP6500AA AF: 0.358 AC: 1578

ESP6500EA AF: 0.218 AC: 1876

ExAC AF: 0.231 AC: 28099

Asia WGS AF: 0.202 AC: 701 AN: 3478

EpiCase AF: 0.203

EpiControl AF: 0.208

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 21307873) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.44
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.00025	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	3.0	N
REVEL	Benign	0.044
Sift	Benign	0.55	T
Sift4G	Benign	1.0	T
Vest4		0.020
MPC		0.56
ClinPred		0.00088	T
GERP RS		1.4
gMVP		0.064

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

LitVar

Other links and lift over

dbSNP: rs707913; hg19: chr6-31084787; COSMIC: COSV52538230; COSMIC: COSV52538230;