rs10903022

chr1-24138623-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_021258.4(IL22RA1):c.135G>A(p.Pro45=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,613,546 control chromosomes in the GnomAD database, including 133,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (11319 hom., cov: 32)
  • Exomes 𝑓: 0.40 (122438 hom.)
• Consequence: IL22RA1 NM_021258.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.57

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 1-24138623-C-T is Benign according to our data. Variant chr1-24138623-C-T is described in ClinVar as [Benign]. Clinvar id is 2688368.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL22RA1	NM_021258.4	c.135G>A	p.Pro45=	synonymous_variant	2/7	ENST00000270800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL22RA1	ENST00000270800.2	c.135G>A	p.Pro45=	synonymous_variant	2/7	1	NM_021258.4	P1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56388 AN: 151844 Hom.: 11321 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.380

GnomAD3 exomes AF: 0.430 AC: 108117 AN: 251290 Hom.: 25188 AF XY: 0.423 AC XY: 57513 AN XY: 135826

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.587

Gnomad ASJ exome AF: 0.321

Gnomad EAS exome AF: 0.736

Gnomad SAS exome AF: 0.467

Gnomad FIN exome AF: 0.357

Gnomad NFE exome AF: 0.372

Gnomad OTH exome AF: 0.397

GnomAD4 exome AF: 0.402 AC: 587087 AN: 1461584 Hom.: 122438 Cov.: 41 AF XY: 0.402 AC XY: 292208 AN XY: 727100

Gnomad4 AFR exome AF: 0.254

Gnomad4 AMR exome AF: 0.575

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.371 AC: 56402 AN: 151962 Hom.: 11319 Cov.: 32 AF XY: 0.375 AC XY: 27850 AN XY: 74242

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.376

Alfa AF: 0.371 Hom.: 17921

Bravo AF: 0.377

Asia WGS AF: 0.587 AC: 2041 AN: 3478

EpiCase AF: 0.361

EpiControl AF: 0.363

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 74% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	2.1
Dann	Benign	0.65

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: rs10903022; hg19: chr1-24465113; COSMIC: COSV54627958;