IL20RA p.Val259Leu

Variant names:

• chr6-137004710-C-A
• rs1555498
• NM_014432.4:c.775G>T
• IL20RA p.Val259Leu

Your query was ambiguous. Multiple possible variants found:

• chr6-137004710-C-A
• chr6-137004710-C-G
• chr6-137004708-TAC-CAA
• chr6-137004708-TAC-AAG
• chr6-137004708-TAC-GAG
• chr6-137004708-TAC-CAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014432.4(IL20RA):​c.775G>T​(p.Val259Leu) 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. 16/22 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: 27)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL20RA NM_014432.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• Publications: 41 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07324225).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014432.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL20RA	NM_014432.4	MANE Select	c.775G>T	p.Val259Leu	missense	Exon 6 of 7	NP_055247.4
	IL20RA	NM_001278722.2		c.628G>T	p.Val210Leu	missense	Exon 6 of 7	NP_001265651.2	Q9UHF4-3
	IL20RA	NM_001278723.3		c.442G>T	p.Val148Leu	missense	Exon 5 of 6	NP_001265652.2	Q9UHF4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL20RA	ENST00000316649.10	TSL:1 MANE Select	c.775G>T	p.Val259Leu	missense	Exon 6 of 7	ENSP00000314976.5	Q9UHF4-1
	IL20RA	ENST00000367748.4	TSL:1	c.442G>T	p.Val148Leu	missense	Exon 5 of 6	ENSP00000356722.1	Q9UHF4-2
	IL20RA	ENST00000878901.1		c.778G>T	p.Val260Leu	missense	Exon 6 of 7	ENSP00000548960.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1458254 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 725246

African (AFR) AF: 0.00 AC: 0 AN: 33310

American (AMR) AF: 0.00 AC: 0 AN: 43938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110850

Other (OTH) AF: 0.00 AC: 0 AN: 60294

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 158617

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.8
DANN	Benign	0.88
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.44
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.082
Sift	Benign	0.16	T
Sift4G	Benign	0.23	T
Varity_R		0.050
gMVP		0.40
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1555498;

hg19: chr6-137325847;