NM_001264.5:c.1525C>T

Variant names:

• chr6-31116090-G-A
• rs150958659
• NM_001264.5:c.1525C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001264.5(CDSN):​c.1525C>T​(p.Leu509Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,612,108 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (6 hom.)
• Consequence: CDSN NM_001264.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.76
• Publications: 1 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=-0.52).
• BP6: Variant 6-31116090-G-A is Benign according to our data. Variant chr6-31116090-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 716000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.76 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00214 (326/152318) while in subpopulation NFE AF = 0.00228 (155/68028). AF 95% confidence interval is 0.00199. There are 2 homozygotes in GnomAd4. There are 194 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

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.1525C>T	p.Leu509Leu	synonymous	Exon 2 of 2	NP_001255.4
	PSORS1C1	NM_014068.3	MANE Select	c.-229+1199G>A		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.1525C>T	p.Leu509Leu	synonymous	Exon 2 of 2	ENSP00000365465.2	Q15517
	PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.-229+1199G>A		intron	N/A	ENSP00000259881.9	Q9UIG5-1
	PSORS1C1	ENST00000479581.5	TSL:1	n.61+1199G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00214 AC: 326 AN: 152200 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00207 AC: 510 AN: 246322 AF XY: 0.00198

Gnomad AFR exome AF: 0.000396

Gnomad AMR exome AF: 0.000406

Gnomad ASJ exome AF: 0.00142

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0103

Gnomad NFE exome AF: 0.00206

Gnomad OTH exome AF: 0.00264

GnomAD4 exome AF: 0.00165 AC: 2414 AN: 1459790 Hom.: 6 Cov.: 58 AF XY: 0.00166 AC XY: 1206 AN XY: 726096

African (AFR) AF: 0.000179 AC: 6 AN: 33470

American (AMR) AF: 0.000604 AC: 27 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000767 AC: 20 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.000395 AC: 34 AN: 86178

European-Finnish (FIN) AF: 0.00916 AC: 479 AN: 52302

Middle Eastern (MID) AF: 0.000721 AC: 4 AN: 5548

European-Non Finnish (NFE) AF: 0.00160 AC: 1776 AN: 1111528

Other (OTH) AF: 0.00113 AC: 68 AN: 60308

GnomAD4 genome AF: 0.00214 AC: 326 AN: 152318 Hom.: 2 Cov.: 31 AF XY: 0.00261 AC XY: 194 AN XY: 74472

African (AFR) AF: 0.000241 AC: 10 AN: 41574

American (AMR) AF: 0.000654 AC: 10 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.0129 AC: 137 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00228 AC: 155 AN: 68028

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00206 Hom.: 1

Bravo AF: 0.00116

EpiCase AF: 0.00229

EpiControl AF: 0.00213

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypotrichosis 2;C1849193:Peeling skin syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.3
DANN	Benign	0.88
PhyloP100		1.8
Mutation Taster		=99/1	polymorphism

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: rs150958659; hg19: chr6-31083867; COSMIC: COSV52540226; COSMIC: COSV52540226;