rs3094212

Variant names:

• chr6-31117993-G-A
• rs3094212
• NM_001264.5:c.86-464C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001264.5(CDSN):​c.86-464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 172,064 control chromosomes in the GnomAD database, including 29,182 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (26168 hom., cov: 31)
  • Exomes 𝑓: 0.52 (3014 hom.)
• Consequence: CDSN NM_001264.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDSN	NM_001264.5	c.86-464C>T		intron_variant	Intron 1 of 1	ENST00000376288.3	NP_001255.4
PSORS1C1	NM_014068.3	c.-229+3102G>A		intron_variant	Intron 1 of 5	ENST00000259881.10	NP_054787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDSN	ENST00000376288.3	c.86-464C>T		intron_variant	Intron 1 of 1	1	NM_001264.5	ENSP00000365465.2
PSORS1C1	ENST00000259881.10	c.-229+3102G>A		intron_variant	Intron 1 of 5	1	NM_014068.3	ENSP00000259881.9

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88064 AN: 151804 Hom.: 26152 Cov.: 31

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.600

GnomAD4 exome AF: 0.518 AC: 10442 AN: 20142 Hom.: 3014 Cov.: 0 AF XY: 0.523 AC XY: 5600 AN XY: 10716

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.588

Gnomad4 ASJ exome AF: 0.610

Gnomad4 EAS exome AF: 0.673

Gnomad4 SAS exome AF: 0.631

Gnomad4 FIN exome AF: 0.408

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.486

GnomAD4 genome AF: 0.580 AC: 88122 AN: 151922 Hom.: 26168 Cov.: 31 AF XY: 0.584 AC XY: 43338 AN XY: 74260

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.599

Alfa AF: 0.540 Hom.: 43250

Bravo AF: 0.594

Asia WGS AF: 0.640 AC: 2227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.0
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs3094212; hg19: chr6-31085770;