1-24138623-C-T

Variant names:

• chr1-24138623-C-T
• rs10903022
• NM_021258.4:c.135G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_021258.4(IL22RA1):​c.135G>A​(p.Pro45Pro) 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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
IL22RA1	NM_021258.4	c.135G>A	p.Pro45Pro	synonymous_variant	Exon 2 of 7	ENST00000270800.2	NP_067081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL22RA1	ENST00000270800.2	c.135G>A	p.Pro45Pro	synonymous_variant	Exon 2 of 7	1	NM_021258.4	ENSP00000270800.1

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

GnomAD2 exomes AF: 0.430 AC: 108117 AN: 251290 AF XY: 0.423

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 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

African (AFR) AF: 0.254 AC: 8510 AN: 33472

American (AMR) AF: 0.575 AC: 25703 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 8421 AN: 26132

East Asian (EAS) AF: 0.738 AC: 29281 AN: 39698

South Asian (SAS) AF: 0.458 AC: 39468 AN: 86252

European-Finnish (FIN) AF: 0.357 AC: 19079 AN: 53414

Middle Eastern (MID) AF: 0.285 AC: 1643 AN: 5766

European-Non Finnish (NFE) AF: 0.388 AC: 430862 AN: 1111756

Other (OTH) AF: 0.399 AC: 24120 AN: 60382

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

African (AFR) AF: 0.267 AC: 11074 AN: 41466

American (AMR) AF: 0.484 AC: 7378 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1130 AN: 3470

East Asian (EAS) AF: 0.745 AC: 3820 AN: 5130

South Asian (SAS) AF: 0.483 AC: 2330 AN: 4820

European-Finnish (FIN) AF: 0.358 AC: 3780 AN: 10560

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25643 AN: 67944

Other (OTH) AF: 0.376 AC: 795 AN: 2112

Alfa AF: 0.371 Hom.: 21667

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

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