rs4713436

Variant names:

• chr6-31116862-C-T
• rs4713436
• NM_001264.5:c.753G>A

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.753G>A​(p.Arg251Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,613,678 control chromosomes in the GnomAD database, including 27,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2457 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25498 hom.)
• Consequence: CDSN NM_001264.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.577
• Publications: 23 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=-0.59).
• BP6: Variant 6-31116862-C-T is Benign according to our data. Variant chr6-31116862-C-T is described in ClinVar as Benign. ClinVar VariationId is 1237033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.577 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDSN	NM_001264.5	MANE Select	c.753G>A	p.Arg251Arg	synonymous	Exon 2 of 2	NP_001255.4
	PSORS1C1	NM_014068.3	MANE Select	c.-229+1971C>T		intron	N/A	NP_054787.2	Q9UIG5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDSN	ENST00000376288.3	TSL:1 MANE Select	c.753G>A	p.Arg251Arg	synonymous	Exon 2 of 2	ENSP00000365465.2	Q15517
	PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.-229+1971C>T		intron	N/A	ENSP00000259881.9	Q9UIG5-1
	PSORS1C1	ENST00000479581.5	TSL:1	n.61+1971C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25956 AN: 152010 Hom.: 2461 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.188

GnomAD2 exomes AF: 0.208 AC: 51547 AN: 248348 AF XY: 0.216

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.211

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.190

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.179 AC: 260910 AN: 1461550 Hom.: 25498 Cov.: 70 AF XY: 0.185 AC XY: 134589 AN XY: 727066

African (AFR) AF: 0.111 AC: 3711 AN: 33476

American (AMR) AF: 0.195 AC: 8716 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 6966 AN: 26132

East Asian (EAS) AF: 0.199 AC: 7916 AN: 39698

South Asian (SAS) AF: 0.327 AC: 28181 AN: 86250

European-Finnish (FIN) AF: 0.196 AC: 10437 AN: 53368

Middle Eastern (MID) AF: 0.248 AC: 1430 AN: 5768

European-Non Finnish (NFE) AF: 0.164 AC: 182585 AN: 1111790

Other (OTH) AF: 0.182 AC: 10968 AN: 60378

GnomAD4 genome AF: 0.171 AC: 25949 AN: 152128 Hom.: 2457 Cov.: 32 AF XY: 0.177 AC XY: 13133 AN XY: 74352

African (AFR) AF: 0.107 AC: 4452 AN: 41528

American (AMR) AF: 0.206 AC: 3140 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3466

East Asian (EAS) AF: 0.200 AC: 1032 AN: 5166

South Asian (SAS) AF: 0.329 AC: 1584 AN: 4812

European-Finnish (FIN) AF: 0.195 AC: 2066 AN: 10580

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12100 AN: 67980

Other (OTH) AF: 0.187 AC: 395 AN: 2112

Alfa AF: 0.177 Hom.: 6018

Bravo AF: 0.165

Asia WGS AF: 0.286 AC: 996 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	-0.59
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		0.58
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4713436; hg19: chr6-31084639; COSMIC: COSV52537811; COSMIC: COSV52537811;