1-67240217-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_144701.3(IL23R):c.1084G>A(p.Val362Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,612,506 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 14 hom., cov: 33)

Exomes 𝑓: 0.013 ( 157 hom. )

Consequence

IL23R
NM_144701.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.808

Publications

40 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=0.0030460954).

BP6

Variant 1-67240217-G-A is Benign according to our data. Variant chr1-67240217-G-A is described in ClinVar as Benign. ClinVar VariationId is 1165955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.01 (1524/152200) while in subpopulation AMR AF = 0.0171 (261/15288). AF 95% confidence interval is 0.0154. There are 14 homozygotes in GnomAd4. There are 695 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	NM_144701.3 link	c.1084G>A	p.Val362Ile	missense_variant	Exon 9 of 11	ENST00000347310.10	NP_653302.2	Q5VWK5-1
IL23R	XM_011540790.4 link	c.1084G>A	p.Val362Ile	missense_variant	Exon 9 of 11		XP_011539092.1	Q5VWK5-1
IL23R	XM_011540791.4 link	c.1084G>A	p.Val362Ile	missense_variant	Exon 9 of 11		XP_011539093.1	Q5VWK5-1
IL23R	XM_047447227.1 link	c.1084G>A	p.Val362Ile	missense_variant	Exon 9 of 11		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10 link	c.1084G>A	p.Val362Ile	missense_variant	Exon 9 of 11	1	NM_144701.3	ENSP00000321345.5		Q5VWK5-1

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

1525

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.0230

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00457

Gnomad FIN

AF:

0.00180

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0148

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.0111

AC:

2778

AN:

251222

AF XY:

0.0116

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.0224

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.0167

Gnomad OTH exome

AF:

0.0144

GnomAD4 exome

AF:

0.0127

AC:

18492

AN:

1460306

Hom.:

157

Cov.:

AF XY:

0.0125

AC XY:

9080

AN XY:

726596

show subpopulations

African (AFR)

AF:

0.00218

AC:

AN:

33464

American (AMR)

AF:

0.0109

AC:

487

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0227

AC:

593

AN:

26114

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39670

South Asian (SAS)

AF:

0.00479

AC:

413

AN:

86236

European-Finnish (FIN)

AF:

0.00261

AC:

139

AN:

53326

Middle Eastern (MID)

AF:

0.0151

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0143

AC:

15904

AN:

1110704

Other (OTH)

AF:

0.0131

AC:

793

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

837

1675

2512

3350

4187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.0100

AC:

1524

AN:

152200

Hom.:

Cov.:

AF XY:

0.00934

AC XY:

695

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00262

AC:

109

AN:

41538

American (AMR)

AF:

0.0171

AC:

261

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0230

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00436

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00180

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0148

AC:

1005

AN:

67998

Other (OTH)

AF:

0.00993

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

154

230

307

384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0143

Hom.:

Bravo

AF:

0.0119

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0149

AC:

128

ExAC

AF:

0.0117

AC:

1415

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0165

EpiControl

AF:

0.0174

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IL23R: BP4, BS1, BS2 -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.17

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.061

.;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.26

T;T;T

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N;.

PhyloP100

-0.81

PrimateAI

Benign

0.30

PROVEAN

Benign

0.060

.;N;.

REVEL

Benign

0.022

Sift

Benign

0.30

.;T;.

Sift4G

Benign

0.30

.;T;T

Polyphen

0.0010, 0.0060

.;B;B

Vest4

0.14, 0.015

MPC

0.13

ClinPred

0.0026

GERP RS

-6.2

Varity_R

0.033

gMVP

0.16

Mutation Taster

=97/3

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over