6-31115879-G-A

Variant names:

• chr6-31115879-G-A
• rs3094217
• NM_001264.5:c.*146C>T

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.*146C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 676,110 control chromosomes in the GnomAD database, including 101,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26021 hom., cov: 30)
  • Exomes 𝑓: 0.53 (75374 hom.)
• Consequence: CDSN NM_001264.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.147
• Publications: 28 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=-0.87).
• BP6: Variant 6-31115879-G-A is Benign according to our data. Variant chr6-31115879-G-A is described in ClinVar as Benign. ClinVar VariationId is 1266446.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 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.*146C>T		3_prime_UTR	Exon 2 of 2	NP_001255.4
	PSORS1C1	NM_014068.3	MANE Select	c.-229+988G>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.*146C>T		3_prime_UTR	Exon 2 of 2	ENSP00000365465.2	Q15517
	PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.-229+988G>A		intron	N/A	ENSP00000259881.9	Q9UIG5-1
	PSORS1C1	ENST00000479581.5	TSL:1	n.61+988G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87787 AN: 151560 Hom.: 26005 Cov.: 30

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.527 AC: 276277 AN: 524432 Hom.: 75374 Cov.: 6 AF XY: 0.531 AC XY: 146184 AN XY: 275154

African (AFR) AF: 0.660 AC: 9553 AN: 14466

American (AMR) AF: 0.556 AC: 15346 AN: 27624

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 9910 AN: 15730

East Asian (EAS) AF: 0.674 AC: 21531 AN: 31956

South Asian (SAS) AF: 0.611 AC: 30835 AN: 50436

European-Finnish (FIN) AF: 0.498 AC: 20300 AN: 40746

Middle Eastern (MID) AF: 0.628 AC: 1362 AN: 2170

European-Non Finnish (NFE) AF: 0.487 AC: 152126 AN: 312654

Other (OTH) AF: 0.535 AC: 15314 AN: 28650

GnomAD4 genome AF: 0.579 AC: 87845 AN: 151678 Hom.: 26021 Cov.: 30 AF XY: 0.582 AC XY: 43167 AN XY: 74116

African (AFR) AF: 0.682 AC: 28157 AN: 41316

American (AMR) AF: 0.616 AC: 9413 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2321 AN: 3462

East Asian (EAS) AF: 0.715 AC: 3663 AN: 5120

South Asian (SAS) AF: 0.617 AC: 2974 AN: 4818

European-Finnish (FIN) AF: 0.500 AC: 5257 AN: 10512

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 34246 AN: 67866

Other (OTH) AF: 0.598 AC: 1261 AN: 2110

Alfa AF: 0.537 Hom.: 86845

Bravo AF: 0.594

Asia WGS AF: 0.640 AC: 2226 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.87
CADD	Benign	4.4
DANN	Benign	0.51
PhyloP100		-0.15
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: rs3094217; hg19: chr6-31083656; COSMIC: COSV52540464; COSMIC: COSV52540464;