rs7530511

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144701.3(IL23R):​c.929T>C​(p.Leu310Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 1,613,024 control chromosomes in the GnomAD database, including 621,497 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L310T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.85 ( 55026 hom., cov: 31)
Exomes 𝑓: 0.88 ( 566471 hom. )

Consequence

IL23R
NM_144701.3 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.37

Publications

119 publications found
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]
C1orf141 (HGNC:32044): (chromosome 1 open reading frame 141)

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_144701.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=7.2443993E-7).
BP6
Variant 1-67219704-T-C is Benign according to our data. Variant chr1-67219704-T-C is described in ClinVar as Benign. ClinVar VariationId is 1169786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144701.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
IL23R
NM_144701.3
MANE Select
c.929T>Cp.Leu310Pro
missense
Exon 7 of 11NP_653302.2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
IL23R
ENST00000347310.10
TSL:1 MANE Select
c.929T>Cp.Leu310Pro
missense
Exon 7 of 11ENSP00000321345.5Q5VWK5-1
IL23R
ENST00000425614.3
TSL:1
c.164T>Cp.Leu55Pro
missense
Exon 2 of 6ENSP00000387640.2Q5VWK5-6
IL23R
ENST00000473881.2
TSL:1
n.164T>C
non_coding_transcript_exon
Exon 2 of 4ENSP00000486667.1A0A0D9SFJ7

Frequencies

GnomAD3 genomes
AF:
0.848
AC:
128970
AN:
152018
Hom.:
54990
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.769
Gnomad AMI
AF:
0.921
Gnomad AMR
AF:
0.869
Gnomad ASJ
AF:
0.901
Gnomad EAS
AF:
0.986
Gnomad SAS
AF:
0.935
Gnomad FIN
AF:
0.856
Gnomad MID
AF:
0.864
Gnomad NFE
AF:
0.870
Gnomad OTH
AF:
0.848
GnomAD2 exomes
AF:
0.883
AC:
221943
AN:
251350
AF XY:
0.886
show subpopulations
Gnomad AFR exome
AF:
0.769
Gnomad AMR exome
AF:
0.913
Gnomad ASJ exome
AF:
0.897
Gnomad EAS exome
AF:
0.986
Gnomad FIN exome
AF:
0.844
Gnomad NFE exome
AF:
0.867
Gnomad OTH exome
AF:
0.879
GnomAD4 exome
AF:
0.880
AC:
1285433
AN:
1460888
Hom.:
566471
Cov.:
46
AF XY:
0.881
AC XY:
640508
AN XY:
726824
show subpopulations
African (AFR)
AF:
0.763
AC:
25500
AN:
33440
American (AMR)
AF:
0.906
AC:
40522
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.896
AC:
23419
AN:
26132
East Asian (EAS)
AF:
0.987
AC:
39180
AN:
39694
South Asian (SAS)
AF:
0.932
AC:
80370
AN:
86250
European-Finnish (FIN)
AF:
0.841
AC:
44923
AN:
53408
Middle Eastern (MID)
AF:
0.864
AC:
4980
AN:
5762
European-Non Finnish (NFE)
AF:
0.876
AC:
973363
AN:
1111110
Other (OTH)
AF:
0.881
AC:
53176
AN:
60370
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.459
Heterozygous variant carriers
0
7725
15450
23174
30899
38624
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
21324
42648
63972
85296
106620
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.848
AC:
129061
AN:
152136
Hom.:
55026
Cov.:
31
AF XY:
0.850
AC XY:
63210
AN XY:
74340
show subpopulations
African (AFR)
AF:
0.769
AC:
31934
AN:
41510
American (AMR)
AF:
0.870
AC:
13288
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.901
AC:
3129
AN:
3472
East Asian (EAS)
AF:
0.986
AC:
5097
AN:
5170
South Asian (SAS)
AF:
0.934
AC:
4492
AN:
4810
European-Finnish (FIN)
AF:
0.856
AC:
9052
AN:
10574
Middle Eastern (MID)
AF:
0.871
AC:
256
AN:
294
European-Non Finnish (NFE)
AF:
0.870
AC:
59183
AN:
68004
Other (OTH)
AF:
0.849
AC:
1794
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
963
1925
2888
3850
4813
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
894
1788
2682
3576
4470
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.866
Hom.:
218510
Bravo
AF:
0.846
Asia WGS
AF:
0.958
AC:
3332
AN:
3478
EpiCase
AF:
0.880
EpiControl
AF:
0.878

ClinVar

ClinVar submissions
Significance:Benign
Revision:criteria provided, multiple submitters, no conflicts
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
-
2
not provided (2)
-
-
1
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.035
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
11
DANN
Benign
0.066
DEOGEN2
Benign
0.073
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.00073
N
LIST_S2
Benign
0.090
T
MetaRNN
Benign
7.2e-7
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-2.7
N
PhyloP100
2.4
PrimateAI
Benign
0.35
T
PROVEAN
Benign
3.7
N
REVEL
Benign
0.19
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
PromoterAI
0.021
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.12
gMVP
0.31
Mutation Taster
=98/2
polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

Other links and lift over

dbSNP: rs7530511;
hg19: chr1-67685387;
COSMIC: COSV107419264;
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.