1-24120978-G-C

Variant names:

• chr1-24120978-G-C
• rs3795299
• NM_021258.4:c.1552C>G

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 the same amino acid substitution has been previously reported as Likely benign in 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 rank	MANE	Protein	UniProt
IL22RA1	NM_021258.4	c.1552C>G	p.Arg518Gly	missense_variant	Exon 7 of 7	ENST00000270800.2	NP_067081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL22RA1	ENST00000270800.2	c.1552C>G	p.Arg518Gly	missense_variant	Exon 7 of 7	1	NM_021258.4	ENSP00000270800.1

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

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 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
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;