6-31116036-T-C

Variant names:

• chr6-31116036-T-C
• rs3130981
• NM_001264.5:c.1579A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001264.5(CDSN):​c.1579A>G​(p.Asn527Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,606,800 control chromosomes in the GnomAD database, including 456,313 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (47124 hom., cov: 31)
  • Exomes 𝑓: 0.75 (409189 hom.)
• Consequence: CDSN NM_001264.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00400
• Publications: 52 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.6709565E-7).
• BP6: Variant 6-31116036-T-C is Benign according to our data. Variant chr6-31116036-T-C is described in ClinVar as Benign. ClinVar VariationId is 1209846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDSN	NM_001264.5	c.1579A>G	p.Asn527Asp	missense_variant	Exon 2 of 2	ENST00000376288.3	NP_001255.4
PSORS1C1	NM_014068.3	c.-229+1145T>C		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.1579A>G	p.Asn527Asp	missense_variant	Exon 2 of 2	1	NM_001264.5	ENSP00000365465.2
PSORS1C1	ENST00000259881.10	c.-229+1145T>C		intron_variant	Intron 1 of 5	1	NM_014068.3	ENSP00000259881.9

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118757 AN: 151792 Hom.: 47082 Cov.: 31

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.775

GnomAD2 exomes AF: 0.758 AC: 185183 AN: 244312 AF XY: 0.763

Gnomad AFR exome AF: 0.898

Gnomad AMR exome AF: 0.687

Gnomad ASJ exome AF: 0.824

Gnomad EAS exome AF: 0.891

Gnomad FIN exome AF: 0.636

Gnomad NFE exome AF: 0.734

Gnomad OTH exome AF: 0.772

GnomAD4 exome AF: 0.748 AC: 1088003 AN: 1454890 Hom.: 409189 Cov.: 45 AF XY: 0.751 AC XY: 543475 AN XY: 723624

African (AFR) AF: 0.899 AC: 30032 AN: 33418

American (AMR) AF: 0.698 AC: 31030 AN: 44472

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 21271 AN: 25928

East Asian (EAS) AF: 0.872 AC: 34576 AN: 39670

South Asian (SAS) AF: 0.833 AC: 71432 AN: 85804

European-Finnish (FIN) AF: 0.639 AC: 33339 AN: 52134

Middle Eastern (MID) AF: 0.819 AC: 4068 AN: 4970

European-Non Finnish (NFE) AF: 0.737 AC: 816505 AN: 1108402

Other (OTH) AF: 0.761 AC: 45750 AN: 60092

GnomAD4 genome AF: 0.782 AC: 118851 AN: 151910 Hom.: 47124 Cov.: 31 AF XY: 0.779 AC XY: 57846 AN XY: 74228

African (AFR) AF: 0.897 AC: 37208 AN: 41460

American (AMR) AF: 0.753 AC: 11508 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2849 AN: 3464

East Asian (EAS) AF: 0.883 AC: 4542 AN: 5142

South Asian (SAS) AF: 0.836 AC: 4018 AN: 4808

European-Finnish (FIN) AF: 0.630 AC: 6643 AN: 10540

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.731 AC: 49627 AN: 67914

Other (OTH) AF: 0.772 AC: 1626 AN: 2106

Alfa AF: 0.758 Hom.: 127772

Bravo AF: 0.796

TwinsUK AF: 0.745 AC: 2761

ALSPAC AF: 0.741 AC: 2854

ESP6500AA AF: 0.899 AC: 3222

ESP6500EA AF: 0.750 AC: 5395

ExAC AF: 0.761 AC: 89564

Asia WGS AF: 0.808 AC: 2810 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 16, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Peeling skin syndrome 1 Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.75
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00073	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	8.7e-7	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.0040
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.032
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.014
MPC		0.35
ClinPred		0.0034	T
GERP RS		-1.2
gMVP		0.040
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: rs3130981; hg19: chr6-31083813;