rs1342642

chr6-137002076-G-A

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IL20RA	NM_014432.4	c.1144C>T	p.Leu382Phe	missense_variant	7/7	ENST00000316649.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL20RA	ENST00000316649.10	c.1144C>T	p.Leu382Phe	missense_variant	7/7	1	NM_014432.4	P1
IL20RA	ENST00000367748.4	c.811C>T	p.Leu271Phe	missense_variant	6/6	1
IL20RA	ENST00000541547.5	c.997C>T	p.Leu333Phe	missense_variant	7/7	2

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

GnomAD3 exomes AF: 0.216 AC: 54356 AN: 251316 Hom.: 6494 AF XY: 0.222 AC XY: 30206 AN XY: 135836

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 SAS exome AF: 0.238

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

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.0675

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.242

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

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.0672

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.254

Alfa AF: 0.253 Hom.: 11622

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
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
MutationTaster	Benign	1.0	P;P;P
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1342642; hg19: chr6-137323213; COSMIC: COSV57358376; COSMIC: COSV57358376;