rs56899166

Positions:

• chr6-31116020-ACTT-A
• chr6-31116020-ACTT-ACTTCTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001264.5(CDSN):​c.*2_*4delAAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,601,398 control chromosomes in the GnomAD database, including 218,877 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26102 hom., cov: 0)
  • Exomes 𝑓: 0.51 (192775 hom.)
• Consequence: CDSN NM_001264.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 -10 ACMG points.

• BP6: Variant 6-31116020-ACTT-A is Benign according to our data. Variant chr6-31116020-ACTT-A is described in ClinVar as [Benign]. Clinvar id is 1302787.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-31116020-ACTT-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDSN	NM_001264.5	c.*2_*4delAAG		3_prime_UTR_variant	2/2	ENST00000376288.3	NP_001255.4
PSORS1C1	NM_014068.3	c.-229+1133_-229+1135delCTT		intron_variant		ENST00000259881.10	NP_054787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDSN	ENST00000376288	c.*2_*4delAAG		3_prime_UTR_variant	2/2	1	NM_001264.5	ENSP00000365465.2
PSORS1C1	ENST00000259881.10	c.-229+1133_-229+1135delCTT		intron_variant		1	NM_014068.3	ENSP00000259881.9

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87916 AN: 151624 Hom.: 26085 Cov.: 0

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.598

GnomAD3 exomes AF: 0.574 AC: 139463 AN: 243122 Hom.: 41342 AF XY: 0.574 AC XY: 76086 AN XY: 132458

Gnomad AFR exome AF: 0.680

Gnomad AMR exome AF: 0.588

Gnomad ASJ exome AF: 0.664

Gnomad EAS exome AF: 0.723

Gnomad SAS exome AF: 0.643

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.508 AC: 736628 AN: 1449654 Hom.: 192775 AF XY: 0.513 AC XY: 370316 AN XY: 721250

Gnomad4 AFR exome AF: 0.675

Gnomad4 AMR exome AF: 0.592

Gnomad4 ASJ exome AF: 0.659

Gnomad4 EAS exome AF: 0.681

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.508

Gnomad4 NFE exome AF: 0.479

Gnomad4 OTH exome AF: 0.524

GnomAD4 genome AF: 0.580 AC: 87976 AN: 151744 Hom.: 26102 Cov.: 0 AF XY: 0.583 AC XY: 43242 AN XY: 74144

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.597

Alfa AF: 0.552 Hom.: 4294

Bravo AF: 0.594

Asia WGS AF: 0.640 AC: 2225 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

GeneDx

Oct 27, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs56899166; hg19: chr6-31083797;