rs3132554

Positions:

• chr6-31116386-A-G
• chr6-31116386-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001264.5(CDSN):​c.1229T>C​(p.Leu410Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,603,348 control chromosomes in the GnomAD database, including 217,911 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 0.58 (26123 hom., cov: 31)
  • Exomes 𝑓: 0.51 (191788 hom.)
• Consequence: CDSN NM_001264.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.368

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]

PSORS1C1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.5814186E-6).
• BP6: Variant 6-31116386-A-G is Benign according to our data. Variant chr6-31116386-A-G is described in ClinVar as [Benign]. Clinvar id is 1600234.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-31116386-A-G is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
CDSN	NM_001264.5	c.1229T>C	p.Leu410Ser	missense_variant	2/2	ENST00000376288.3	NP_001255.4
PSORS1C1	NM_014068.3	c.-229+1495A>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.1229T>C	p.Leu410Ser	missense_variant	2/2	1	NM_001264.5	ENSP00000365465.2
PSORS1C1	ENST00000259881.10	c.-229+1495A>G		intron_variant		1	NM_014068.3	ENSP00000259881.9

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87962 AN: 151652 Hom.: 26108 Cov.: 31

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.387

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: 0.690

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.600

GnomAD3 exomes AF: 0.571 AC: 132540 AN: 232242 Hom.: 38416 AF XY: 0.571 AC XY: 71596 AN XY: 125400

Gnomad AFR exome AF: 0.677

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.658

Gnomad EAS exome AF: 0.720

Gnomad SAS exome AF: 0.639

Gnomad FIN exome AF: 0.509

Gnomad NFE exome AF: 0.510

Gnomad OTH exome AF: 0.586

GnomAD4 exome AF: 0.508 AC: 738095 AN: 1451580 Hom.: 191788 Cov.: 69 AF XY: 0.514 AC XY: 370440 AN XY: 721312

Gnomad4 AFR exome AF: 0.676

Gnomad4 AMR exome AF: 0.589

Gnomad4 ASJ exome AF: 0.658

Gnomad4 EAS exome AF: 0.680

Gnomad4 SAS exome AF: 0.635

Gnomad4 FIN exome AF: 0.508

Gnomad4 NFE exome AF: 0.479

Gnomad4 OTH exome AF: 0.525

GnomAD4 genome AF: 0.580 AC: 88018 AN: 151768 Hom.: 26123 Cov.: 31 AF XY: 0.584 AC XY: 43273 AN XY: 74152

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.599

Alfa AF: 0.537 Hom.: 14072

Bravo AF: 0.594

TwinsUK AF: 0.475 AC: 1761

ALSPAC AF: 0.455 AC: 1753

ESP6500AA AF: 0.662 AC: 2918

ESP6500EA AF: 0.508 AC: 4371

ExAC AF: 0.561 AC: 67864

Asia WGS AF: 0.640 AC: 2227 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.3
DANN	Benign	0.68
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.00076	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0000046	T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.029
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.025
MPC		0.43
ClinPred		0.0070	T
GERP RS		1.4
gMVP		0.042

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: rs3132554; hg19: chr6-31084163; COSMIC: COSV52537557; COSMIC: COSV52537557;