Variant 1-24121577-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021258.4(IL22RA1):c.953G>A(p.Arg318Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000875 in 1,611,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

IL22RA1
NM_021258.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.12

Variant links:

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]

IL22RA1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020074159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL22RA1	NM_021258.4 linkuse as main transcript	c.953G>A	p.Arg318Gln	missense_variant	7/7	ENST00000270800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL22RA1	ENST00000270800.2 linkuse as main transcript	c.953G>A	p.Arg318Gln	missense_variant	7/7	1	NM_021258.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000799

AC:

AN:

250176

Hom.:

AF XY:

0.0000888

AC XY:

AN XY:

135176

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000904

AC:

132

AN:

1459908

Hom.:

Cov.:

AF XY:

0.0000868

AC XY:

AN XY:

725994

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000954

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.953G>A (p.R318Q) alteration is located in exon 7 (coding exon 7) of the IL22RA1 gene. This alteration results from a G to A substitution at nucleotide position 953, causing the arginine (R) at amino acid position 318 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.92

Cadd

Benign

0.0040

Dann

Benign

0.85

DEOGEN2

Benign

0.018

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.60

M_CAP

Benign

0.0042

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

0.14

REVEL

Benign

0.0080

Sift

Benign

0.35

Sift4G

Benign

0.46

Polyphen

0.0010

Vest4

0.046

MutPred

0.076

Loss of phosphorylation at S320 (P = 0.0705);

MVP

0.067

MPC

0.13

ClinPred

0.024

GERP RS

-7.7

Varity_R

0.021

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over