NM_144701.3:c.1142G>A

Variant names:

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.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. 12/21 in silico tools predict 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

Clinical Significance

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

Conservation

PhyloP100: 2.74

Publications

606 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	NM_144701.3	MANE Select	c.1142G>A	p.Arg381Gln	missense	Exon 9 of 11	NP_653302.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IL23R	ENST00000347310.10	TSL:1 MANE Select	c.1142G>A	p.Arg381Gln	missense	Exon 9 of 11	ENSP00000321345.5
IL23R	ENST00000425614.3	TSL:1	c.377G>A	p.Arg126Gln	missense	Exon 4 of 6	ENSP00000387640.2
IL23R	ENST00000637002.1	TSL:1	n.*603G>A		non_coding_transcript_exon	Exon 9 of 11	ENSP00000490340.2

Frequencies

GnomAD3 genomes

AF:

0.0458

AC:

6971

AN:

152044

Hom.:

217

Cov.:

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

GnomAD2 exomes

AF:

0.0422

AC:

10589

AN:

250900

AF XY:

0.0426

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 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.:

AF XY:

0.0548

AC XY:

39655

AN XY:

723268

show subpopulations

African (AFR)

AF:

0.0102

AC:

339

AN:

33348

American (AMR)

AF:

0.0360

AC:

1610

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0716

AC:

1866

AN:

26052

East Asian (EAS)

AF:

0.000101

AC:

AN:

39616

South Asian (SAS)

AF:

0.0145

AC:

1247

AN:

86064

European-Finnish (FIN)

AF:

0.0482

AC:

2565

AN:

53170

Middle Eastern (MID)

AF:

0.0514

AC:

291

AN:

5658

European-Non Finnish (NFE)

AF:

0.0635

AC:

70095

AN:

1103968

Other (OTH)

AF:

0.0495

AC:

2973

AN:

60070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

3294

6588

9881

13175

16469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2608

5216

7824

10432

13040

<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:

0.0458

AC:

6970

AN:

152162

Hom.:

217

Cov.:

AF XY:

0.0450

AC XY:

3350

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0125

AC:

519

AN:

41494

American (AMR)

AF:

0.0509

AC:

779

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0711

AC:

247

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.0137

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0599

AC:

633

AN:

10574

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0664

AC:

4519

AN:

68008

Other (OTH)

AF:

0.0468

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

344

688

1033

1377

1721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0587

Hom.:

1484

Bravo

AF:

0.0450

TwinsUK

AF:

0.0631

AC:

234

ALSPAC

AF:

0.0706

AC:

272

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.0637

AC:

548

ExAC

AF:

0.0415

AC:

5038

Asia WGS

AF:

0.00982

AC:

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Inflammatory bowel disease 17, protection against

Benign:1

Apr 01, 2010

OMIM

Significance:protective

Review Status:no assertion criteria provided

Collection Method:literature only

Psoriasis, protection against

Benign:1

Apr 01, 2010

OMIM

Significance:protective

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.5

PhyloP100

2.7

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.2

REVEL

Benign

0.18

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.24

MPC

0.59

ClinPred

0.033

GERP RS

5.2

Varity_R

0.35

gMVP

0.43

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over