rs1342642

Variant names:

• chr6-137002076-G-A
• rs1342642
• NM_014432.4:c.1144C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014432.4(IL20RA):​c.1144C>T​(p.Leu382Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,613,872 control chromosomes in the GnomAD database, including 50,866 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4096 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46770 hom.)
• Consequence: IL20RA NM_014432.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 30 publications found

Genes affected

IL20RA (HGNC:6003): (interleukin 20 receptor subunit alpha) This gene encodes a member of the type II cytokine receptor family. The encoded protein is a subunit of the receptor for interleukin 20, a cytokine that may be involved in epidermal function. The interleukin 20 receptor is a heterodimeric complex consisting of the encoded protein and interleukin 20 receptor beta. This gene and interleukin 20 receptor beta are highly expressed in skin, and are upregulated in psoriasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005023539).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL20RA	NM_014432.4	c.1144C>T	p.Leu382Phe	missense_variant	Exon 7 of 7	ENST00000316649.10	NP_055247.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL20RA	ENST00000316649.10	c.1144C>T	p.Leu382Phe	missense_variant	Exon 7 of 7	1	NM_014432.4	ENSP00000314976.5
IL20RA	ENST00000367748.4	c.811C>T	p.Leu271Phe	missense_variant	Exon 6 of 6	1		ENSP00000356722.1
IL20RA	ENST00000541547.5	c.997C>T	p.Leu333Phe	missense_variant	Exon 7 of 7	2		ENSP00000437843.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34489 AN: 151948 Hom.: 4091 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0668

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.256

GnomAD2 exomes AF: 0.216 AC: 54356 AN: 251316 AF XY: 0.222

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.0660

Gnomad FIN exome AF: 0.181

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.249 AC: 364025 AN: 1461806 Hom.: 46770 Cov.: 35 AF XY: 0.250 AC XY: 181522 AN XY: 727214

African (AFR) AF: 0.217 AC: 7268 AN: 33480

American (AMR) AF: 0.147 AC: 6579 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5896 AN: 26136

East Asian (EAS) AF: 0.0675 AC: 2680 AN: 39700

South Asian (SAS) AF: 0.232 AC: 19993 AN: 86256

European-Finnish (FIN) AF: 0.185 AC: 9868 AN: 53412

Middle Eastern (MID) AF: 0.268 AC: 1544 AN: 5768

European-Non Finnish (NFE) AF: 0.266 AC: 295605 AN: 1111936

Other (OTH) AF: 0.242 AC: 14592 AN: 60394

GnomAD4 genome AF: 0.227 AC: 34517 AN: 152066 Hom.: 4096 Cov.: 32 AF XY: 0.220 AC XY: 16371 AN XY: 74326

African (AFR) AF: 0.215 AC: 8905 AN: 41476

American (AMR) AF: 0.194 AC: 2962 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3466

East Asian (EAS) AF: 0.0672 AC: 347 AN: 5166

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4820

European-Finnish (FIN) AF: 0.178 AC: 1886 AN: 10568

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17718 AN: 67976

Other (OTH) AF: 0.254 AC: 536 AN: 2110

Alfa AF: 0.250 Hom.: 15720

Bravo AF: 0.226

TwinsUK AF: 0.258 AC: 955

ALSPAC AF: 0.260 AC: 1001

ESP6500AA AF: 0.222 AC: 977

ESP6500EA AF: 0.270 AC: 2322

ExAC AF: 0.221 AC: 26865

Asia WGS AF: 0.191 AC: 668 AN: 3478

EpiCase AF: 0.262

EpiControl AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	.;T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.56	T;T;T
MetaRNN	Benign	0.0050	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L;.
PhyloP100		0.12
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.068
Sift	Benign	0.078	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.93, 0.90	.;P;P
Vest4		0.038
MPC		0.50
ClinPred		0.013	T
GERP RS		0.25
Varity_R		0.049
gMVP		0.16
Mutation Taster		=96/4	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: rs1342642; hg19: chr6-137323213; COSMIC: COSV57358376; COSMIC: COSV57358376;