dbSNP rs1343151: IL23R:c.1149-2391G>A (chr1-67253446-G-A) – ACMG Classification: Benign (-12 pts)

Germline classification Cancer classification (beta)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BA1BP4_Strong

The NM_144701.3(IL23R):c.1149-2391G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.404 (AC=61,408) in the gnomAD database across 152,018 control chromosomes, including 15,100 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.674. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 15100 hom., cov: 32)

Consequence

IL23R
NM_144701.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0970

Publications

108 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 Gene-Disease associations (from GenCC):

immunodeficiency disease
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
inherited susceptibility to mycobacterial diseases
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

IL23R 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.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6737 — exceeds 5%% threshold (BA1 applied)

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.1149-2391G>A		intron	N/A	NP_653302.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL23R	ENST00000347310.10	TSL:1 MANE Select	c.1149-2391G>A	intron	N/A	ENSP00000321345.5	Q5VWK5-1
IL23R	ENST00000425614.3	TSL:1	c.384-2391G>A	intron	N/A	ENSP00000387640.2	Q5VWK5-6
IL23R	ENST00000473881.2	TSL:1	n.191-2391G>A	intron	N/A	ENSP00000486667.1	A0A0D9SFJ7

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61345

AN:

151900

Hom.:

15079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.0550

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.364

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.404

AC:

61408

AN:

152018

Hom.:

15100

Cov.:

AF XY:

0.390

AC XY:

28946

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.680

AC:

28212

AN:

41468

American (AMR)

AF:

0.290

AC:

4431

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

1037

AN:

3470

East Asian (EAS)

AF:

0.0547

AC:

283

AN:

5174

South Asian (SAS)

AF:

0.150

AC:

721

AN:

4816

European-Finnish (FIN)

AF:

0.211

AC:

2230

AN:

10550

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.342

AC:

23269

AN:

67952

Other (OTH)

AF:

0.362

AC:

763

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1627

3254

4881

6508

8135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.364

Hom.:

39712

Bravo

AF:

0.423

Asia WGS

AF:

0.179

AC:

625

AN:

3476

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.105

AC:

12889

AN:

122680

Turkish Variome

AF:

0.281

AC:

434

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.0301

AC:

270

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.403

AC:

944

AN:

2342

Hom.:

195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.9

(source)

DANN

Benign

0.83

PhyloP100

-0.097

Mutation Taster

=100/0

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

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over