3-136991971-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144717.4(IL20RB):c.565C>A(p.Pro189Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IL20RB NM_144717.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

Genes affected

IL20RB (HGNC:6004): (interleukin 20 receptor subunit beta) IL20RB and IL20RA (MIM 605620) form a heterodimeric receptor for interleukin-20 (IL20; MIM 605619) (Blumberg et al., 2001 [PubMed 11163236]).[supplied by OMIM, Feb 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL20RB	NM_144717.4	c.565C>A	p.Pro189Thr	missense_variant	5/7	ENST00000329582.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL20RB	ENST00000329582.9	c.565C>A	p.Pro189Thr	missense_variant	5/7	1	NM_144717.4	P1
IL20RB	ENST00000475972.1	c.*197C>A		3_prime_UTR_variant, NMD_transcript_variant	5/7	1
IL20RB	ENST00000469964.5	c.*516+2406C>A		intron_variant, NMD_transcript_variant		2
IL20RB	ENST00000491483.5	c.*550C>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461864 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Feb 16, 2023

The c.565C>A (p.P189T) alteration is located in exon 5 (coding exon 5) of the IL20RB gene. This alteration results from a C to A substitution at nucleotide position 565, causing the proline (P) at amino acid position 189 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	12
Dann	Benign	0.20
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.033
Sift	Benign	0.42	T
Sift4G	Benign	0.62	T
Polyphen		0.036	B
Vest4		0.30
MutPred		0.35		Gain of glycosylation at P189 (P = 0.0872);
MVP		0.36
MPC		0.29
ClinPred		0.087	T
GERP RS		2.7
Varity_R		0.18
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.21		Position offset: -33

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

Publications

LitVar

Other links and lift over

dbSNP: rs1942041414; hg19: chr3-136710813;