6-31117187-T-C

Variant names:

• chr6-31117187-T-C
• rs3130984
• NM_001264.5:c.428A>G

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.428A>G​(p.Asn143Ser) 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 1,613,786 control chromosomes in the GnomAD database, including 457,328 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.78 (47225 hom., cov: 34)
  • Exomes 𝑓: 0.75 (410103 hom.)
• Consequence: CDSN NM_001264.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.664
• Publications: 30 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 (MetaRNN=6.526956E-7).
• BP6: Variant 6-31117187-T-C is Benign according to our data. Variant chr6-31117187-T-C is described in ClinVar as [Benign]. Clinvar id is 1544053.Status of the report is criteria_provided_single_submitter, 1 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.428A>G	p.Asn143Ser	missense_variant	Exon 2 of 2	ENST00000376288.3	NP_001255.4
PSORS1C1	NM_014068.3	c.-229+2296T>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.428A>G	p.Asn143Ser	missense_variant	Exon 2 of 2	1	NM_001264.5	ENSP00000365465.2
PSORS1C1	ENST00000259881.10	c.-229+2296T>C		intron_variant	Intron 1 of 5	1	NM_014068.3	ENSP00000259881.9

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118971 AN: 152022 Hom.: 47183 Cov.: 34

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.885

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: 0.756 AC: 187718 AN: 248252 AF XY: 0.761

Gnomad AFR exome AF: 0.897

Gnomad AMR exome AF: 0.687

Gnomad ASJ exome AF: 0.818

Gnomad EAS exome AF: 0.894

Gnomad FIN exome AF: 0.635

Gnomad NFE exome AF: 0.732

Gnomad OTH exome AF: 0.769

GnomAD4 exome AF: 0.747 AC: 1092295 AN: 1461646 Hom.: 410103 Cov.: 75 AF XY: 0.751 AC XY: 545701 AN XY: 727108

African (AFR) AF: 0.898 AC: 30076 AN: 33478

American (AMR) AF: 0.697 AC: 31161 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 21383 AN: 26134

East Asian (EAS) AF: 0.873 AC: 34661 AN: 39696

South Asian (SAS) AF: 0.831 AC: 71679 AN: 86252

European-Finnish (FIN) AF: 0.640 AC: 34122 AN: 53350

Middle Eastern (MID) AF: 0.820 AC: 4730 AN: 5768

European-Non Finnish (NFE) AF: 0.736 AC: 818536 AN: 1111872

Other (OTH) AF: 0.761 AC: 45947 AN: 60386

GnomAD4 genome AF: 0.783 AC: 119065 AN: 152140 Hom.: 47225 Cov.: 34 AF XY: 0.780 AC XY: 57963 AN XY: 74356

African (AFR) AF: 0.898 AC: 37286 AN: 41544

American (AMR) AF: 0.753 AC: 11528 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2853 AN: 3468

East Asian (EAS) AF: 0.886 AC: 4583 AN: 5174

South Asian (SAS) AF: 0.835 AC: 4027 AN: 4820

European-Finnish (FIN) AF: 0.630 AC: 6660 AN: 10566

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

European-Non Finnish (NFE) AF: 0.731 AC: 49665 AN: 67956

Other (OTH) AF: 0.773 AC: 1630 AN: 2110

Alfa AF: 0.758 Hom.: 72438

Bravo AF: 0.796

TwinsUK AF: 0.744 AC: 2758

ALSPAC AF: 0.740 AC: 2852

ESP6500AA AF: 0.888 AC: 3892

ESP6500EA AF: 0.733 AC: 6275

ExAC AF: 0.761 AC: 92081

Asia WGS AF: 0.809 AC: 2813 AN: 3478

EpiCase AF: 0.737

EpiControl AF: 0.744

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.043
DANN	Benign	0.38
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00035	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	6.5e-7	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.66
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.013
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.044
MPC		0.25
ClinPred		0.000030	T
GERP RS		0.77
gMVP		0.065
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: rs3130984; hg19: chr6-31084964; COSMIC: COSV52539647; COSMIC: COSV52539647;