Variant chr6-137004748-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014432.4(IL20RA):c.737A>G(p.Glu246Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL20RA
NM_014432.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10875881).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL20RA	NM_014432.4 linkuse as main transcript	c.737A>G	p.Glu246Gly	missense_variant	6/7	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.737A>G	p.Glu246Gly	missense_variant	6/7	1	NM_014432.4	ENSP00000314976.5	Q9UHF4-1
IL20RA	ENST00000367748.4 linkuse as main transcript	c.404A>G	p.Glu135Gly	missense_variant	5/6	1		ENSP00000356722.1	Q9UHF4-2
IL20RA	ENST00000541547.5 linkuse as main transcript	c.590A>G	p.Glu197Gly	missense_variant	6/7	2		ENSP00000437843.1	Q9UHF4-3
IL20RA	ENST00000468393.5 linkuse as main transcript	c.404A>G	p.Glu135Gly	missense_variant	5/5	4		ENSP00000489177.1	A0A0U1RQU9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000532

AC:

AN:

188138

Hom.:

AF XY:

0.00

AC XY:

AN XY:

103474

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000241

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.97e-7

AC:

AN:

1433982

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713038

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

Alfa

AF:

0.000112

Hom.:

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

Nov 13, 2024

The c.737A>G (p.E246G) alteration is located in exon 6 (coding exon 6) of the IL20RA gene. This alteration results from a A to G substitution at nucleotide position 737, causing the glutamic acid (E) at amino acid position 246 to be replaced by a glycine (G). 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

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0084

.;T;.;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.77

N;N;N;.

REVEL

Benign

0.086

Sift

Benign

0.19

T;T;T;.

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.15, 0.40

.;B;B;.

Vest4

0.14

MutPred

0.49

.;Loss of ubiquitination at K241 (P = 0.0255);.;.;

MVP

0.63

MPC

0.37

ClinPred

0.25

GERP RS

2.0

Varity_R

0.092

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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