1-24120978-G-C

Position:

• chr1-24120978-G-C

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.1552C>G​(p.Arg518Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,613,892 control chromosomes in the GnomAD database, including 143,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.38 (11826 hom., cov: 33)
  • Exomes 𝑓: 0.42 (131370 hom.)
• Consequence: IL22RA1 NM_021258.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.88

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 (MetaRNN=3.006041E-6).
• BP6: Variant 1-24120978-G-C is Benign according to our data. Variant chr1-24120978-G-C is described in ClinVar as [Benign]. Clinvar id is 2688377.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL22RA1	NM_021258.4	c.1552C>G	p.Arg518Gly	missense_variant	7/7	ENST00000270800.2	NP_067081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL22RA1	ENST00000270800.2	c.1552C>G	p.Arg518Gly	missense_variant	7/7	1	NM_021258.4	ENSP00000270800	P1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58488 AN: 151996 Hom.: 11827 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.399

GnomAD3 exomes AF: 0.419 AC: 105330 AN: 251216 Hom.: 23296 AF XY: 0.423 AC XY: 57370 AN XY: 135762

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.413

Gnomad ASJ exome AF: 0.382

Gnomad EAS exome AF: 0.702

Gnomad SAS exome AF: 0.513

Gnomad FIN exome AF: 0.312

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.398

GnomAD4 exome AF: 0.418 AC: 610955 AN: 1461778 Hom.: 131370 Cov.: 63 AF XY: 0.420 AC XY: 305292 AN XY: 727188

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.719

Gnomad4 SAS exome AF: 0.507

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.410

Gnomad4 OTH exome AF: 0.424

GnomAD4 genome AF: 0.385 AC: 58495 AN: 152114 Hom.: 11826 Cov.: 33 AF XY: 0.386 AC XY: 28669 AN XY: 74340

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.395

Alfa AF: 0.386 Hom.: 7236

Bravo AF: 0.386

TwinsUK AF: 0.398 AC: 1476

ALSPAC AF: 0.409 AC: 1575

ESP6500AA AF: 0.304 AC: 1339

ESP6500EA AF: 0.408 AC: 3507

ExAC AF: 0.417 AC: 50655

Asia WGS AF: 0.576 AC: 2001 AN: 3478

EpiCase AF: 0.393

EpiControl AF: 0.394

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 66% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0000030	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.088
Sift	Benign	0.26	T
Sift4G	Benign	0.090	T
Polyphen		0.18	B
Vest4		0.027
MPC		0.18
ClinPred		0.0098	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.066
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs3795299; hg19: chr1-24447468; COSMIC: COSV54628228;