chr6-137004710-C-A

Position:

• chr6-137004710-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V259I) has been classified as Likely benign.

• 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

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

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=0.07324225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL20RA	NM_014432.4	c.775G>T	p.Val259Leu	missense_variant	6/7	ENST00000316649.10	NP_055247.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL20RA	ENST00000316649.10	c.775G>T	p.Val259Leu	missense_variant	6/7	1	NM_014432.4	ENSP00000314976	P1
IL20RA	ENST00000367748.4	c.442G>T	p.Val148Leu	missense_variant	5/6	1		ENSP00000356722
IL20RA	ENST00000541547.5	c.628G>T	p.Val210Leu	missense_variant	6/7	2		ENSP00000437843
IL20RA	ENST00000468393.5	c.442G>T	p.Val148Leu	missense_variant	5/5	4		ENSP00000489177

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

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: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.073	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;N;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.61	N;N;N;.
REVEL	Benign	0.082
Sift	Benign	0.16	T;T;T;.
Sift4G	Benign	0.23	T;T;T;T
Polyphen		0.019, 0.013	.;B;B;.
Vest4		0.14
MutPred		0.40		.;Loss of sheet (P = 0.0817);.;.;
MVP		0.28
MPC		0.27
ClinPred		0.30	T
GERP RS		-0.049
Varity_R		0.050
gMVP		0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555498; hg19: chr6-137325847;