Variant 6-137001934-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014432.4(IL20RA):c.1286G>A(p.Gly429Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,614,136 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 2 hom. )

Consequence

IL20RA
NM_014432.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.293

Variant links:

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]

IL20RA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020582646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL20RA	NM_014432.4 linkuse as main transcript	c.1286G>A	p.Gly429Glu	missense_variant	7/7	ENST00000316649.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL20RA	ENST00000316649.10 linkuse as main transcript	c.1286G>A	p.Gly429Glu	missense_variant	7/7	1	NM_014432.4	P1	Q9UHF4-1
IL20RA	ENST00000367748.4 linkuse as main transcript	c.953G>A	p.Gly318Glu	missense_variant	6/6	1			Q9UHF4-2
IL20RA	ENST00000541547.5 linkuse as main transcript	c.1139G>A	p.Gly380Glu	missense_variant	7/7	2			Q9UHF4-3

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000127

AC:

AN:

251356

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000118

AC:

172

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000116

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000315

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000152

Hom.:

Bravo

AF:

0.000370

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 20, 2023

The c.1286G>A (p.G429E) alteration is located in exon 7 (coding exon 7) of the IL20RA gene. This alteration results from a G to A substitution at nucleotide position 1286, causing the glycine (G) at amino acid position 429 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.51

Cadd

Benign

6.9

Dann

Benign

0.74

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.083

Sift

Benign

0.56

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.41, 0.93

.;B;P

Vest4

0.018

MVP

0.77

MPC

0.38

ClinPred

0.014

GERP RS

3.9

Varity_R

0.047

gMVP

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over