rs11209026

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144701.3(IL23R):​c.1142G>A​(p.Arg381Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0548 in 1,604,812 control chromosomes in the GnomAD database, including 2,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 217 hom., cov: 33)
Exomes 𝑓: 0.056 ( 2622 hom. )

Consequence

IL23R
NM_144701.3 missense

Scores

3
5
10

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.74
Variant links:
Genes affected
IL23R (HGNC:19100): (interleukin 23 receptor) The protein encoded by this gene is a subunit of the receptor for IL23A/IL23. This protein pairs with the receptor molecule IL12RB1/IL12Rbeta1, and both are required for IL23A signaling. This protein associates constitutively with Janus kinase 2 (JAK2), and also binds to transcription activator STAT3 in a ligand-dependent manner. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0025800169).
BP6
Variant 1-67240275-G-A is Benign according to our data. Variant chr1-67240275-G-A is described in ClinVar as [Benign]. Clinvar id is 3108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL23RNM_144701.3 linkuse as main transcriptc.1142G>A p.Arg381Gln missense_variant 9/11 ENST00000347310.10 NP_653302.2
IL23RXM_011540790.4 linkuse as main transcriptc.1142G>A p.Arg381Gln missense_variant 9/11 XP_011539092.1
IL23RXM_011540791.4 linkuse as main transcriptc.1142G>A p.Arg381Gln missense_variant 9/11 XP_011539093.1
IL23RXM_047447227.1 linkuse as main transcriptc.1142G>A p.Arg381Gln missense_variant 9/11 XP_047303183.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL23RENST00000347310.10 linkuse as main transcriptc.1142G>A p.Arg381Gln missense_variant 9/111 NM_144701.3 ENSP00000321345 P1Q5VWK5-1

Frequencies

GnomAD3 genomes
AF:
0.0458
AC:
6971
AN:
152044
Hom.:
217
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0125
Gnomad AMI
AF:
0.102
Gnomad AMR
AF:
0.0510
Gnomad ASJ
AF:
0.0711
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.0135
Gnomad FIN
AF:
0.0599
Gnomad MID
AF:
0.0506
Gnomad NFE
AF:
0.0665
Gnomad OTH
AF:
0.0473
GnomAD3 exomes
AF:
0.0422
AC:
10589
AN:
250900
Hom.:
306
AF XY:
0.0426
AC XY:
5771
AN XY:
135628
show subpopulations
Gnomad AFR exome
AF:
0.0113
Gnomad AMR exome
AF:
0.0359
Gnomad ASJ exome
AF:
0.0687
Gnomad EAS exome
AF:
0.000327
Gnomad SAS exome
AF:
0.0151
Gnomad FIN exome
AF:
0.0500
Gnomad NFE exome
AF:
0.0586
Gnomad OTH exome
AF:
0.0456
GnomAD4 exome
AF:
0.0558
AC:
80990
AN:
1452650
Hom.:
2622
Cov.:
28
AF XY:
0.0548
AC XY:
39655
AN XY:
723268
show subpopulations
Gnomad4 AFR exome
AF:
0.0102
Gnomad4 AMR exome
AF:
0.0360
Gnomad4 ASJ exome
AF:
0.0716
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0145
Gnomad4 FIN exome
AF:
0.0482
Gnomad4 NFE exome
AF:
0.0635
Gnomad4 OTH exome
AF:
0.0495
GnomAD4 genome
AF:
0.0458
AC:
6970
AN:
152162
Hom.:
217
Cov.:
33
AF XY:
0.0450
AC XY:
3350
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0125
Gnomad4 AMR
AF:
0.0509
Gnomad4 ASJ
AF:
0.0711
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.0137
Gnomad4 FIN
AF:
0.0599
Gnomad4 NFE
AF:
0.0664
Gnomad4 OTH
AF:
0.0468
Alfa
AF:
0.0610
Hom.:
812
Bravo
AF:
0.0450
TwinsUK
AF:
0.0631
AC:
234
ALSPAC
AF:
0.0706
AC:
272
ESP6500AA
AF:
0.0141
AC:
62
ESP6500EA
AF:
0.0637
AC:
548
ExAC
AF:
0.0415
AC:
5038
Asia WGS
AF:
0.00982
AC:
34
AN:
3478
EpiCase
AF:
0.0682
EpiControl
AF:
0.0672

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Inflammatory bowel disease 17, protection against Benign:1
protective, no assertion criteria providedliterature onlyOMIMApr 01, 2010- -
Psoriasis, protection against Benign:1
protective, no assertion criteria providedliterature onlyOMIMApr 01, 2010- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.37
.;T;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Uncertain
0.88
D;D;D
MetaRNN
Benign
0.0026
T;T;T
MetaSVM
Benign
-0.60
T
MutationAssessor
Uncertain
2.5
.;M;.
MutationTaster
Benign
0.56
D;D;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.2
.;N;.
REVEL
Benign
0.18
Sift
Pathogenic
0.0
.;D;.
Sift4G
Pathogenic
0.0
.;D;D
Polyphen
1.0
.;D;D
Vest4
0.24, 0.17
MPC
0.59
ClinPred
0.033
T
GERP RS
5.2
Varity_R
0.35
gMVP
0.43

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

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

Other links and lift over

dbSNP: rs11209026; hg19: chr1-67705958; COSMIC: COSV61373825; API