1-24121256-A-T

Variant summary

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

The NM_021258.4(IL22RA1):​c.1274T>A​(p.Leu425His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

IL22RA1
NM_021258.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.134
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]

Genome browser will be placed here

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=0.060035676).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL22RA1NM_021258.4 linkuse as main transcriptc.1274T>A p.Leu425His missense_variant 7/7 ENST00000270800.2 NP_067081.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL22RA1ENST00000270800.2 linkuse as main transcriptc.1274T>A p.Leu425His missense_variant 7/71 NM_021258.4 ENSP00000270800 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsJan 23, 2024The c.1274T>A (p.L425H) alteration is located in exon 7 (coding exon 7) of the IL22RA1 gene. This alteration results from a T to A substitution at nucleotide position 1274, causing the leucine (L) at amino acid position 425 to be replaced by a histidine (H). 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
0.089
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.047
T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.45
T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.060
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.0
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.067
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.036
D
Polyphen
0.025
B
Vest4
0.17
MutPred
0.079
Loss of stability (P = 0.0961);
MVP
0.15
MPC
0.15
ClinPred
0.35
T
GERP RS
2.2
Varity_R
0.18
gMVP
0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-24447746; API