6-31116020-ACTT-A

Variant names:

• chr6-31116020-ACTT-A
• rs56899166
• NM_001264.5:c.*2_*4delAAG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001264.5(CDSN):​c.*2_*4delAAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,601,398 control chromosomes in the GnomAD database, including 218,877 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26102 hom., cov: 0)
  • Exomes 𝑓: 0.51 (192775 hom.)
• Consequence: CDSN NM_001264.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• 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 -10 ACMG points.

• BP6: Variant 6-31116020-ACTT-A is Benign according to our data. Variant chr6-31116020-ACTT-A is described in ClinVar as Benign. ClinVar VariationId is 1302787.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDSN	NM_001264.5	c.*2_*4delAAG		3_prime_UTR_variant	Exon 2 of 2	ENST00000376288.3	NP_001255.4
PSORS1C1	NM_014068.3	c.-229+1133_-229+1135delCTT		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.*2_*4delAAG		3_prime_UTR_variant	Exon 2 of 2	1	NM_001264.5	ENSP00000365465.2
PSORS1C1	ENST00000259881.10	c.-229+1133_-229+1135delCTT		intron_variant	Intron 1 of 5	1	NM_014068.3	ENSP00000259881.9

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87916 AN: 151624 Hom.: 26085 Cov.: 0

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.598

GnomAD2 exomes AF: 0.574 AC: 139463 AN: 243122 AF XY: 0.574

Gnomad AFR exome AF: 0.680

Gnomad AMR exome AF: 0.588

Gnomad ASJ exome AF: 0.664

Gnomad EAS exome AF: 0.723

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.508 AC: 736628 AN: 1449654 Hom.: 192775 AF XY: 0.513 AC XY: 370316 AN XY: 721250

African (AFR) AF: 0.675 AC: 22441 AN: 33236

American (AMR) AF: 0.592 AC: 26241 AN: 44328

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 17015 AN: 25838

East Asian (EAS) AF: 0.681 AC: 26982 AN: 39630

South Asian (SAS) AF: 0.636 AC: 54390 AN: 85568

European-Finnish (FIN) AF: 0.508 AC: 26496 AN: 52108

Middle Eastern (MID) AF: 0.667 AC: 3173 AN: 4754

European-Non Finnish (NFE) AF: 0.479 AC: 528478 AN: 1104272

Other (OTH) AF: 0.524 AC: 31412 AN: 59920

GnomAD4 genome AF: 0.580 AC: 87976 AN: 151744 Hom.: 26102 Cov.: 0 AF XY: 0.583 AC XY: 43242 AN XY: 74144

African (AFR) AF: 0.682 AC: 28225 AN: 41360

American (AMR) AF: 0.616 AC: 9405 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2323 AN: 3464

East Asian (EAS) AF: 0.717 AC: 3677 AN: 5130

South Asian (SAS) AF: 0.618 AC: 2977 AN: 4814

European-Finnish (FIN) AF: 0.503 AC: 5292 AN: 10528

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

European-Non Finnish (NFE) AF: 0.505 AC: 34273 AN: 67886

Other (OTH) AF: 0.597 AC: 1253 AN: 2100

Alfa AF: 0.552 Hom.: 4294

Bravo AF: 0.594

Asia WGS AF: 0.640 AC: 2225 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 27, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
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: rs56899166; hg19: chr6-31083797; COSMIC: COSV52537114; COSMIC: COSV52537114;