6-137004710-C-T

Variant names:

• chr6-137004710-C-T
• rs1555498
• NM_014432.4:c.775G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014432.4(IL20RA):​c.775G>A​(p.Val259Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 1,609,136 control chromosomes in the GnomAD database, including 767,584 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.86 (59247 hom., cov: 27)
  • Exomes 𝑓: 0.98 (708337 hom.)
• Consequence: IL20RA NM_014432.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• Publications: 41 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.5179483E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL20RA	NM_014432.4	c.775G>A	p.Val259Ile	missense_variant	Exon 6 of 7	ENST00000316649.10	NP_055247.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL20RA	ENST00000316649.10	c.775G>A	p.Val259Ile	missense_variant	Exon 6 of 7	1	NM_014432.4	ENSP00000314976.5
IL20RA	ENST00000367748.4	c.442G>A	p.Val148Ile	missense_variant	Exon 5 of 6	1		ENSP00000356722.1
IL20RA	ENST00000541547.5	c.628G>A	p.Val210Ile	missense_variant	Exon 6 of 7	2		ENSP00000437843.1
IL20RA	ENST00000468393.5	c.442G>A	p.Val148Ile	missense_variant	Exon 5 of 5	4		ENSP00000489177.1

Frequencies

GnomAD3 genomes AF: 0.862 AC: 130008 AN: 150856 Hom.: 59249 Cov.: 27

Gnomad AFR AF: 0.524

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.997

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.882

GnomAD2 exomes AF: 0.960 AC: 238185 AN: 248028 AF XY: 0.970

Gnomad AFR exome AF: 0.515

Gnomad AMR exome AF: 0.970

Gnomad ASJ exome AF: 0.975

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.996

Gnomad OTH exome AF: 0.972

GnomAD4 exome AF: 0.983 AC: 1432849 AN: 1458162 Hom.: 708337 Cov.: 35 AF XY: 0.984 AC XY: 713877 AN XY: 725202

African (AFR) AF: 0.498 AC: 16548 AN: 33250

American (AMR) AF: 0.967 AC: 42493 AN: 43924

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 25430 AN: 26072

East Asian (EAS) AF: 1.00 AC: 39665 AN: 39682

South Asian (SAS) AF: 0.997 AC: 84727 AN: 84946

European-Finnish (FIN) AF: 1.00 AC: 53397 AN: 53400

Middle Eastern (MID) AF: 0.947 AC: 5459 AN: 5762

European-Non Finnish (NFE) AF: 0.997 AC: 1107260 AN: 1110836

Other (OTH) AF: 0.960 AC: 57870 AN: 60290

GnomAD4 genome AF: 0.861 AC: 130032 AN: 150974 Hom.: 59247 Cov.: 27 AF XY: 0.865 AC XY: 63787 AN XY: 73738

African (AFR) AF: 0.523 AC: 21266 AN: 40676

American (AMR) AF: 0.942 AC: 14337 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 3393 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5146 AN: 5150

South Asian (SAS) AF: 0.997 AC: 4777 AN: 4790

European-Finnish (FIN) AF: 1.00 AC: 10389 AN: 10390

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67686 AN: 67976

Other (OTH) AF: 0.879 AC: 1844 AN: 2098

Alfa AF: 0.944 Hom.: 158617

Bravo AF: 0.840

TwinsUK AF: 0.997 AC: 3696

ALSPAC AF: 0.997 AC: 3843

ESP6500AA AF: 0.532 AC: 2342

ESP6500EA AF: 0.993 AC: 8543

ExAC AF: 0.953 AC: 115648

Asia WGS AF: 0.936 AC: 3256 AN: 3478

EpiCase AF: 0.993

EpiControl AF: 0.994

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.012
DANN	Benign	0.18
DEOGEN2	Benign	0.0034	.;T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.40	T;T;T;T
MetaRNN	Benign	6.5e-7	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.2	.;N;.;.
PhyloP100		-0.44
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.14	N;N;N;.
REVEL	Benign	0.079
Sift	Benign	1.0	T;T;T;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0010, 0.0	.;B;B;.
Vest4		0.080
MPC		0.21
ClinPred		0.00030	T
GERP RS		-0.049
Varity_R		0.020
gMVP		0.26
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs1555498; hg19: chr6-137325847; COSMIC: COSV107346361; COSMIC: COSV107346361;