6-137001683-C-T

Variant names:

• chr6-137001683-C-T
• rs200592228
• NM_014432.4:c.1537G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014432.4(IL20RA):​c.1537G>A​(p.Gly513Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,614,142 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (1 hom.)
• Consequence: IL20RA NM_014432.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.00

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 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=0.007883579).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL20RA	NM_014432.4	c.1537G>A	p.Gly513Arg	missense_variant	Exon 7 of 7	ENST00000316649.10	NP_055247.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL20RA	ENST00000316649.10	c.1537G>A	p.Gly513Arg	missense_variant	Exon 7 of 7	1	NM_014432.4	ENSP00000314976.5
IL20RA	ENST00000367748.4	c.1204G>A	p.Gly402Arg	missense_variant	Exon 6 of 6	1		ENSP00000356722.1
IL20RA	ENST00000541547.5	c.1390G>A	p.Gly464Arg	missense_variant	Exon 7 of 7	2		ENSP00000437843.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000175 AC: 44 AN: 251380 Hom.: 1 AF XY: 0.000191 AC XY: 26 AN XY: 135850

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.00208

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000153 AC: 224 AN: 1461858 Hom.: 1 Cov.: 31 AF XY: 0.000138 AC XY: 100 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000140

Gnomad4 OTH exome AF: 0.000232

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74458

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000175 Hom.: 0

Bravo AF: 0.000144

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000198 AC: 24

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1537G>A (p.G513R) alteration is located in exon 7 (coding exon 7) of the IL20RA gene. This alteration results from a G to A substitution at nucleotide position 1537, causing the glycine (G) at amino acid position 513 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	0.083
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.0090
DANN	Benign	0.65
DEOGEN2	Benign	0.0061	.;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.0079	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.21	N;N;N
REVEL	Benign	0.042
Sift	Benign	0.57	T;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		0.41, 0.0010	.;B;B
Vest4		0.18
MutPred		0.34		.;Gain of sheet (P = 0.0125);.;
MVP		0.21
MPC		0.30
ClinPred		0.020	T
GERP RS		-12
Varity_R		0.040
gMVP		0.12

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

Other links and lift over

dbSNP: rs200592228; hg19: chr6-137322820; COSMIC: COSV104608899; COSMIC: COSV104608899;