6-31116658-G-A

Variant names:

• chr6-31116658-G-A
• rs1062470
• NM_001264.5:c.957C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001264.5(CDSN):​c.957C>T​(p.Tyr319Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,612,366 control chromosomes in the GnomAD database, including 95,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13543 hom., cov: 32)
  • Exomes 𝑓: 0.33 (82448 hom.)
• Consequence: CDSN NM_001264.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.15
• Publications: 60 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 6-31116658-G-A is Benign according to our data. Variant chr6-31116658-G-A is described in ClinVar as Benign. ClinVar VariationId is 1643739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.15 with no splicing effect.
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDSN	NM_001264.5	MANE Select	c.957C>T	p.Tyr319Tyr	synonymous	Exon 2 of 2	NP_001255.4
	PSORS1C1	NM_014068.3	MANE Select	c.-229+1767G>A		intron	N/A	NP_054787.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDSN	ENST00000376288.3	TSL:1 MANE Select	c.957C>T	p.Tyr319Tyr	synonymous	Exon 2 of 2	ENSP00000365465.2
	PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.-229+1767G>A		intron	N/A	ENSP00000259881.9
	PSORS1C1	ENST00000479581.5	TSL:1	n.61+1767G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62101 AN: 151920 Hom.: 13528 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.413

GnomAD2 exomes AF: 0.366 AC: 89592 AN: 244670 AF XY: 0.358

Gnomad AFR exome AF: 0.571

Gnomad AMR exome AF: 0.397

Gnomad ASJ exome AF: 0.389

Gnomad EAS exome AF: 0.513

Gnomad FIN exome AF: 0.315

Gnomad NFE exome AF: 0.326

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.331 AC: 482923 AN: 1460328 Hom.: 82448 Cov.: 71 AF XY: 0.329 AC XY: 239207 AN XY: 726394

African (AFR) AF: 0.565 AC: 18907 AN: 33474

American (AMR) AF: 0.397 AC: 17736 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 10220 AN: 26136

East Asian (EAS) AF: 0.481 AC: 19113 AN: 39696

South Asian (SAS) AF: 0.308 AC: 26600 AN: 86258

European-Finnish (FIN) AF: 0.313 AC: 16307 AN: 52028

Middle Eastern (MID) AF: 0.430 AC: 2483 AN: 5768

European-Non Finnish (NFE) AF: 0.316 AC: 350812 AN: 1111876

Other (OTH) AF: 0.344 AC: 20745 AN: 60378

GnomAD4 genome AF: 0.409 AC: 62166 AN: 152038 Hom.: 13543 Cov.: 32 AF XY: 0.406 AC XY: 30196 AN XY: 74316

African (AFR) AF: 0.574 AC: 23814 AN: 41456

American (AMR) AF: 0.410 AC: 6270 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3472

East Asian (EAS) AF: 0.517 AC: 2663 AN: 5152

South Asian (SAS) AF: 0.288 AC: 1389 AN: 4824

European-Finnish (FIN) AF: 0.307 AC: 3249 AN: 10590

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22212 AN: 67956

Other (OTH) AF: 0.412 AC: 867 AN: 2104

Alfa AF: 0.354 Hom.: 31463

Bravo AF: 0.428

Asia WGS AF: 0.354 AC: 1230 AN: 3478

EpiCase AF: 0.325

EpiControl AF: 0.327

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.2
DANN	Benign	0.82
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1062470; hg19: chr6-31084435; COSMIC: COSV52538287; COSMIC: COSV52538287;