1-24120724-G-A

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.*81C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,310,466 control chromosomes in the GnomAD database, including 274,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33922 hom., cov: 35)
  • Exomes 𝑓: 0.64 (240872 hom.)
• Consequence: IL22RA1 NM_021258.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75

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=-0.83).
• BP6: Variant 1-24120724-G-A is Benign according to our data. Variant chr1-24120724-G-A is described in ClinVar as [Benign]. Clinvar id is 2688539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL22RA1	NM_021258.4	c.*81C>T		3_prime_UTR_variant	7/7	ENST00000270800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL22RA1	ENST00000270800.2	c.*81C>T		3_prime_UTR_variant	7/7	1	NM_021258.4	P1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100700 AN: 152076 Hom.: 33903 Cov.: 35

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.655

GnomAD4 exome AF: 0.642 AC: 743373 AN: 1158272 Hom.: 240872 Cov.: 15 AF XY: 0.646 AC XY: 371262 AN XY: 575148

Gnomad4 AFR exome AF: 0.780

Gnomad4 AMR exome AF: 0.562

Gnomad4 ASJ exome AF: 0.671

Gnomad4 EAS exome AF: 0.720

Gnomad4 SAS exome AF: 0.786

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.634

Gnomad4 OTH exome AF: 0.658

GnomAD4 genome AF: 0.662 AC: 100760 AN: 152194 Hom.: 33922 Cov.: 35 AF XY: 0.659 AC XY: 48996 AN XY: 74400

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.649

Alfa AF: 0.632 Hom.: 40312

Bravo AF: 0.670

Asia WGS AF: 0.736 AC: 2560 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 85% of patients studied by a panel of primary immunodeficiencies. Number of patients: 75. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.026
Dann	Benign	0.37

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: rs3795300; hg19: chr1-24447214; COSMIC: COSV54627922;