6-31115952-A-C

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.*73T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,354,914 control chromosomes in the GnomAD database, including 78,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13517 hom., cov: 32)
  • Exomes 𝑓: 0.32 (65085 hom.)
• Consequence: CDSN NM_001264.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.157

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-31115952-A-C is Benign according to our data. Variant chr6-31115952-A-C is described in ClinVar as [Benign]. Clinvar id is 1230203.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
CDSN	NM_001264.5	c.*73T>G		3_prime_UTR_variant	2/2	ENST00000376288.3
PSORS1C1	NM_014068.3	c.-229+1061A>C		intron_variant		ENST00000259881.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDSN	ENST00000376288.3	c.*73T>G		3_prime_UTR_variant	2/2	1	NM_001264.5	P1
PSORS1C1	ENST00000259881.10	c.-229+1061A>C		intron_variant		1	NM_014068.3	P2

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62017 AN: 151756 Hom.: 13502 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.322 AC: 386957 AN: 1203040 Hom.: 65085 Cov.: 17 AF XY: 0.321 AC XY: 194722 AN XY: 607060

Gnomad4 AFR exome AF: 0.556

Gnomad4 AMR exome AF: 0.394

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.409 AC: 62082 AN: 151874 Hom.: 13517 Cov.: 32 AF XY: 0.406 AC XY: 30146 AN XY: 74220

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.410

Alfa AF: 0.275 Hom.: 1400

Bravo AF: 0.428

Asia WGS AF: 0.354 AC: 1230 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

Nov 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.1
Dann	Benign	0.79

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: rs3095297; hg19: chr6-31083729; COSMIC: COSV52538282; COSMIC: COSV52538282;