NM_001264.5:c.1344T>C

Variant names:

• chr6-31116271-A-G
• rs3094216
• NM_001264.5:c.1344T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001264.5(CDSN):​c.1344T>C​(p.Cys448Cys) 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
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001264.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDSN	NM_001264.5	MANE Select	c.1344T>C	p.Cys448Cys	synonymous	Exon 2 of 2	NP_001255.4
	PSORS1C1	NM_014068.3	MANE Select	c.-229+1380A>G		intron	N/A	NP_054787.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDSN	ENST00000376288.3	TSL:1 MANE Select	c.1344T>C	p.Cys448Cys	synonymous	Exon 2 of 2	ENSP00000365465.2
	PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.-229+1380A>G		intron	N/A	ENSP00000259881.9
	PSORS1C1	ENST00000479581.5	TSL:1	n.61+1380A>G		intron	N/A

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

GnomAD2 exomes AF: 0.183 AC: 45996 AN: 251238 AF XY: 0.187

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 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

African (AFR) AF: 0.223 AC: 7454 AN: 33480

American (AMR) AF: 0.105 AC: 4708 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 4196 AN: 26134

East Asian (EAS) AF: 0.192 AC: 7630 AN: 39698

South Asian (SAS) AF: 0.196 AC: 16911 AN: 86252

European-Finnish (FIN) AF: 0.130 AC: 6959 AN: 53410

Middle Eastern (MID) AF: 0.142 AC: 817 AN: 5768

European-Non Finnish (NFE) AF: 0.256 AC: 285068 AN: 1111956

Other (OTH) AF: 0.236 AC: 14237 AN: 60394

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

African (AFR) AF: 0.215 AC: 8920 AN: 41476

American (AMR) AF: 0.137 AC: 2089 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3468

East Asian (EAS) AF: 0.167 AC: 857 AN: 5146

South Asian (SAS) AF: 0.217 AC: 1042 AN: 4802

European-Finnish (FIN) AF: 0.127 AC: 1345 AN: 10592

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.226 AC: 15330 AN: 67946

Other (OTH) AF: 0.174 AC: 368 AN: 2110

Alfa AF: 0.220 Hom.: 14102

Bravo AF: 0.202

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.2
DANN	Benign	0.76
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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