Variant 6-137001880-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014432.4(IL20RA):c.1340A>G(p.Gln447Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,854 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

IL20RA
NM_014432.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.744

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016841084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL20RA	NM_014432.4 linkuse as main transcript	c.1340A>G	p.Gln447Arg	missense_variant	7/7	ENST00000316649.10	NP_055247.4	Q9UHF4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL20RA	ENST00000316649.10 linkuse as main transcript	c.1340A>G	p.Gln447Arg	missense_variant	7/7	1	NM_014432.4	ENSP00000314976.5	Q9UHF4-1
IL20RA	ENST00000367748.4 linkuse as main transcript	c.1007A>G	p.Gln336Arg	missense_variant	6/6	1		ENSP00000356722.1	Q9UHF4-2
IL20RA	ENST00000541547.5 linkuse as main transcript	c.1193A>G	p.Gln398Arg	missense_variant	7/7	2		ENSP00000437843.1	Q9UHF4-3

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

250976

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461544

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000989

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000204

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000502

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

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 09, 2024

The c.1340A>G (p.Q447R) alteration is located in exon 7 (coding exon 7) of the IL20RA gene. This alteration results from a A to G substitution at nucleotide position 1340, causing the glutamine (Q) at amino acid position 447 to be replaced by an arginine (R). 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

0.071

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.13

DANN

Benign

0.47

DEOGEN2

Benign

0.0026

.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.49

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

.;N;.

PrimateAI

Benign

0.24

PROVEAN

Benign

0.070

N;N;N

REVEL

Benign

0.0070

Sift

Benign

0.76

T;T;T

Sift4G

Benign

0.72

T;T;T

Polyphen

0.28, 0.53

.;B;P

Vest4

0.023

MVP

0.42

MPC

0.27

ClinPred

0.036

GERP RS

-2.9

Varity_R

0.038

gMVP

0.15

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