Variant 1-206867444-A-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_018724.4(IL20):c.439A>C(p.Ser147Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

IL20
NM_018724.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

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 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=0.12760752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IL20	NM_018724.4 linkuse as main transcript	c.439A>C	p.Ser147Arg	missense_variant	5/6	ENST00000367098.6
IL20	NM_001385166.1 linkuse as main transcript	c.439A>C	p.Ser147Arg	missense_variant	6/7
IL20	NM_001385167.1 linkuse as main transcript	c.439A>C	p.Ser147Arg	missense_variant	7/8
IL20	NM_001385165.1 linkuse as main transcript	c.378+808A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL20	ENST00000367098.6 linkuse as main transcript	c.439A>C	p.Ser147Arg	missense_variant	5/6	1	NM_018724.4	P1	Q9NYY1-1
IL20	ENST00000367096.7 linkuse as main transcript	c.439A>C	p.Ser147Arg	missense_variant	4/5	1		P1	Q9NYY1-1
IL20	ENST00000391930.3 linkuse as main transcript	c.378+808A>C		intron_variant		1			Q9NYY1-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251380

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000595

AC:

AN:

1461440

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000729

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.0000340

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000594

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

Mar 29, 2022

The c.439A>C (p.S147R) alteration is located in exon 4 (coding exon 4) of the IL20 gene. This alteration results from a A to C substitution at nucleotide position 439, causing the serine (S) at amino acid position 147 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

0.15

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.085

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.54

.;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.94

L;L

MutationTaster

Benign

0.94

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.027

Sift

Benign

0.23

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.013

B;B

Vest4

0.27

MutPred

0.42

Loss of ubiquitination at K151 (P = 0.0525);Loss of ubiquitination at K151 (P = 0.0525);

MVP

0.27

MPC

0.17

ClinPred

0.16

GERP RS

4.5

Varity_R

0.21

gMVP

0.25

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