Genetic Variant IL20:p.Val158Ala (chr1-206868506-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_018724.4(IL20):c.473T>C(p.Val158Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,443,636 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IL20
NM_018724.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.181

Variant links:

Genes affected

IL20 (HGNC:6002): (interleukin 20) The protein encoded by this gene is a cytokine structurally related to interleukin 10 (IL10). This cytokine has been shown to transduce its signal through signal transducer and activator of transcription 3 (STAT3) in keratinocytes. A specific receptor for this cytokine is found to be expressed in skin and upregulated dramatically in psoriatic skin, suggesting a role for this protein in epidermal function and psoriasis. [provided by RefSeq, Jul 2008]

IL20 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=0.048045516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL20	NM_018724.4 link	c.473T>C	p.Val158Ala	missense_variant	Exon 6 of 6	ENST00000367098.6	NP_061194.2	Q9NYY1-1A0A7R8C4W0
IL20	NM_001385166.1 link	c.473T>C	p.Val158Ala	missense_variant	Exon 7 of 7		NP_001372095.1
IL20	NM_001385167.1 link	c.473T>C	p.Val158Ala	missense_variant	Exon 8 of 8		NP_001372096.1
IL20	NM_001385165.1 link	c.398T>C	p.Val133Ala	missense_variant	Exon 5 of 5		NP_001372094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL20	ENST00000367098.6 link	c.473T>C	p.Val158Ala	missense_variant	Exon 6 of 6	1	NM_018724.4	ENSP00000356065.1	Q9NYY1-1
IL20	ENST00000367096.7 link	c.473T>C	p.Val158Ala	missense_variant	Exon 5 of 5	1		ENSP00000356063.3	Q9NYY1-1
IL20	ENST00000391930.3 link	c.398T>C	p.Val133Ala	missense_variant	Exon 4 of 4	1		ENSP00000375796.2	Q9NYY1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000422

AC:

AN:

237182

Hom.:

AF XY:

0.00000778

AC XY:

AN XY:

128478

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000601

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:

0.00000139

AC:

AN:

1443636

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717916

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000525

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.473T>C (p.V158A) alteration is located in exon 5 (coding exon 5) of the IL20 gene. This alteration results from a T to C substitution at nucleotide position 473, causing the valine (V) at amino acid position 158 to be replaced by an alanine (A). 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

0.064

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.4

DANN

Benign

0.47

DEOGEN2

Benign

0.082

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.47

.;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.45

N;N;.

PrimateAI

Benign

0.41

PROVEAN

Benign

0.23

N;N;N

REVEL

Benign

0.056

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0050

B;B;.

Vest4

0.11

MutPred

0.67

Gain of ubiquitination at K160 (P = 0.0505);Gain of ubiquitination at K160 (P = 0.0505);.;

MVP

0.19

MPC

0.12

ClinPred

0.014

GERP RS

-1.7

Varity_R

0.069

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

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