6-31116271-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001264.5(CDSN):c.1344T>C(p.Cys448=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,613,834 control chromosomes in the GnomAD database, including 47,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3212 hom., cov: 31)
  • Exomes 𝑓: 0.24 (44091 hom.)
• Consequence: CDSN NM_001264.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.203

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 6-31116271-A-G is Benign according to our data. Variant chr6-31116271-A-G is described in ClinVar as [Benign]. Clinvar id is 1280864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.203 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDSN	NM_001264.5	c.1344T>C	p.Cys448=	synonymous_variant	2/2	ENST00000376288.3
PSORS1C1	NM_014068.3	c.-229+1380A>G		intron_variant		ENST00000259881.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDSN	ENST00000376288.3	c.1344T>C	p.Cys448=	synonymous_variant	2/2	1	NM_001264.5	P1
PSORS1C1	ENST00000259881.10	c.-229+1380A>G		intron_variant		1	NM_014068.3	P2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30720 AN: 151910 Hom.: 3204 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.176

GnomAD3 exomes AF: 0.183 AC: 45996 AN: 251238 Hom.: 4683 AF XY: 0.187 AC XY: 25323 AN XY: 135776

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.0987

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.191

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.238 AC: 347980 AN: 1461808 Hom.: 44091 Cov.: 64 AF XY: 0.236 AC XY: 171652 AN XY: 727204

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.202 AC: 30754 AN: 152026 Hom.: 3212 Cov.: 31 AF XY: 0.196 AC XY: 14555 AN XY: 74322

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.174

Alfa AF: 0.219 Hom.: 6062

Bravo AF: 0.202

Asia WGS AF: 0.169 AC: 587 AN: 3478

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	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	5.2
Dann	Benign	0.76

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: rs3094216; hg19: chr6-31084048; COSMIC: COSV52537195; COSMIC: COSV52537195;