rs4486393

Positions:

• chr1-24137073-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021258.4(IL22RA1):​c.355+58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,539,464 control chromosomes in the GnomAD database, including 38,224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4191 hom., cov: 31)
  • Exomes 𝑓: 0.22 (34033 hom.)
• Consequence: IL22RA1 NM_021258.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.977

Genes affected

IL22RA1 (HGNC:13700): (interleukin 22 receptor subunit alpha 1) The protein encoded by this gene belongs to the class II cytokine receptor family, and has been shown to be a receptor for interleukin 22 (IL22). IL22 receptor is a protein complex that consists of this protein and interleukin 10 receptor, beta (IL10BR/CRFB4), a subunit also shared by the receptor complex for interleukin 10 (IL10). This gene and interleukin 28 receptor, alpha (IL28RA) form a cytokine receptor gene cluster in the chromosomal region 1p36. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-24137073-C-T is Benign according to our data. Variant chr1-24137073-C-T is described in ClinVar as [Benign]. Clinvar id is 2688450.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL22RA1	NM_021258.4	c.355+58G>A		intron_variant		ENST00000270800.2	NP_067081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL22RA1	ENST00000270800.2	c.355+58G>A		intron_variant		1	NM_021258.4	ENSP00000270800.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34261 AN: 151918 Hom.: 4189 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.215 AC: 298802 AN: 1387428 Hom.: 34033 AF XY: 0.217 AC XY: 148606 AN XY: 683452

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.000831

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.226 AC: 34293 AN: 152036 Hom.: 4191 Cov.: 31 AF XY: 0.223 AC XY: 16584 AN XY: 74334

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.215

Alfa AF: 0.215 Hom.: 4699

Bravo AF: 0.222

Asia WGS AF: 0.106 AC: 371 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 31. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.48

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: rs4486393; hg19: chr1-24463563;