rs7530511

Variant names:

Your query was ambiguous. Multiple possible variants found:

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

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]

IL23R links:

C1orf141 (HGNC:32044): (chromosome 1 open reading frame 141)

C1orf141 links:

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	NM_144701.3	MANE Select	c.929T>C	p.Leu310Pro	missense	Exon 7 of 11	NP_653302.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL23R	ENST00000347310.10	TSL:1 MANE Select	c.929T>C	p.Leu310Pro	missense	Exon 7 of 11	ENSP00000321345.5	Q5VWK5-1
IL23R	ENST00000425614.3	TSL:1	c.164T>C	p.Leu55Pro	missense	Exon 2 of 6	ENSP00000387640.2	Q5VWK5-6
IL23R	ENST00000473881.2	TSL:1	n.164T>C		non_coding_transcript_exon	Exon 2 of 4	ENSP00000486667.1	A0A0D9SFJ7

Frequencies

GnomAD3 genomes

AF:

0.848

AC:

128970

AN:

152018

Hom.:

54990

Cov.:

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.:

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

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

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.:

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

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

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

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.035

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.066

DEOGEN2

Benign

0.073

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.00073

LIST_S2

Benign

0.090

MetaRNN

Benign

7.2e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.7

PhyloP100

2.4

PrimateAI

Benign

0.35

PROVEAN

Benign

3.7

REVEL

Benign

0.19

Sift

Benign

1.0

Sift4G

Benign

1.0

PromoterAI

0.021

Neutral

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over