NM_001264.5:c.*73T>G

Variant names:

• chr6-31115952-A-C
• rs3095297
• NM_001264.5:c.*73T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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 -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 VariationId 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.

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.*73T>G		3_prime_UTR	Exon 2 of 2	NP_001255.4
	PSORS1C1	NM_014068.3	MANE Select	c.-229+1061A>C		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.*73T>G		3_prime_UTR	Exon 2 of 2	ENSP00000365465.2	Q15517
	PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.-229+1061A>C		intron	N/A	ENSP00000259881.9	Q9UIG5-1
	PSORS1C1	ENST00000479581.5	TSL:1	n.61+1061A>C		intron	N/A

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

African (AFR) AF: 0.556 AC: 15456 AN: 27782

American (AMR) AF: 0.394 AC: 17103 AN: 43384

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 9228 AN: 23964

East Asian (EAS) AF: 0.481 AC: 18253 AN: 37984

South Asian (SAS) AF: 0.305 AC: 24342 AN: 79856

European-Finnish (FIN) AF: 0.312 AC: 16163 AN: 51800

Middle Eastern (MID) AF: 0.408 AC: 1467 AN: 3596

European-Non Finnish (NFE) AF: 0.303 AC: 267676 AN: 883374

Other (OTH) AF: 0.337 AC: 17269 AN: 51300

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

African (AFR) AF: 0.575 AC: 23756 AN: 41344

American (AMR) AF: 0.410 AC: 6268 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3470

East Asian (EAS) AF: 0.517 AC: 2665 AN: 5154

South Asian (SAS) AF: 0.288 AC: 1386 AN: 4814

European-Finnish (FIN) AF: 0.306 AC: 3237 AN: 10562

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.327 AC: 22203 AN: 67946

Other (OTH) AF: 0.410 AC: 865 AN: 2108

Alfa AF: 0.356 Hom.: 18888

Bravo AF: 0.428

Asia WGS AF: 0.354 AC: 1230 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.79
PhyloP100		0.16
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: rs3095297; hg19: chr6-31083729; COSMIC: COSV52538282; COSMIC: COSV52538282;