chr6-137001686-G-A

Variant names:

• chr6-137001686-G-A
• NM_014432.4:c.1534C>T

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.1534C>T​(p.Leu512Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL20RA NM_014432.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.946
• Publications: 0 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=0.0843606).

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.1534C>T	p.Leu512Phe	missense	Exon 7 of 7	NP_055247.4
	IL20RA	NM_001278722.2		c.1387C>T	p.Leu463Phe	missense	Exon 7 of 7	NP_001265651.2	Q9UHF4-3
	IL20RA	NM_001278723.3		c.1201C>T	p.Leu401Phe	missense	Exon 6 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.1534C>T	p.Leu512Phe	missense	Exon 7 of 7	ENSP00000314976.5	Q9UHF4-1
	IL20RA	ENST00000367748.4	TSL:1	c.1201C>T	p.Leu401Phe	missense	Exon 6 of 6	ENSP00000356722.1	Q9UHF4-2
	IL20RA	ENST00000878901.1		c.1537C>T	p.Leu513Phe	missense	Exon 7 of 7	ENSP00000548960.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.5
DANN	Benign	0.51
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.95
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.10
Sift	Benign	0.23	T
Sift4G	Benign	0.94	T
Polyphen		0.013	B
Vest4		0.057
MutPred		0.18		Gain of sheet (P = 0.0166)
MVP		0.72
MPC		0.29
ClinPred		0.15	T
GERP RS		1.6
Varity_R		0.038
gMVP		0.11
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr6-137322823;