6-137002258-T-C

Position:

• chr6-137002258-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014432.4(IL20RA):​c.962A>G​(p.Lys321Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,614,002 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (2 hom.)
• Consequence: IL20RA NM_014432.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.710

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026730776).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL20RA	NM_014432.4	c.962A>G	p.Lys321Arg	missense_variant	7/7	ENST00000316649.10	NP_055247.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL20RA	ENST00000316649.10	c.962A>G	p.Lys321Arg	missense_variant	7/7	1	NM_014432.4	ENSP00000314976.5
IL20RA	ENST00000367748.4	c.629A>G	p.Lys210Arg	missense_variant	6/6	1		ENSP00000356722.1
IL20RA	ENST00000541547.5	c.815A>G	p.Lys272Arg	missense_variant	7/7	2		ENSP00000437843.1

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000268 AC: 67 AN: 249968 Hom.: 0 AF XY: 0.000214 AC XY: 29 AN XY: 135398

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000926

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000214

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000136 AC: 199 AN: 1461690 Hom.: 2 Cov.: 31 AF XY: 0.000127 AC XY: 92 AN XY: 727164

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000107

Gnomad4 OTH exome AF: 0.000315

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74482

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000235 Hom.: 0

Bravo AF: 0.000215

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000280 AC: 34

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 31, 2024

The c.962A>G (p.K321R) alteration is located in exon 7 (coding exon 7) of the IL20RA gene. This alteration results from a A to G substitution at nucleotide position 962, causing the lysine (K) at amino acid position 321 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	0.075
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	.;T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.027	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.027
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.58, 0.86	.;P;P
Vest4		0.027
MVP		0.78
MPC		0.26
ClinPred		0.016	T
GERP RS		2.2
Varity_R		0.063
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs143552862; hg19: chr6-137323395;