Genetic Variant IL23R:c.1045+41T>G (chr1-67236843-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144701.3(IL23R):c.1045+41T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 1,294,446 control chromosomes in the GnomAD database, including 2,260 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.053 ( 251 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2009 hom. )

Consequence

IL23R
NM_144701.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0420

Publications

134 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0607 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.1045+41T>G		intron	N/A	NP_653302.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL23R	ENST00000347310.10	TSL:1 MANE Select	c.1045+41T>G	intron	N/A	ENSP00000321345.5
IL23R	ENST00000425614.3	TSL:1	c.280+41T>G	intron	N/A	ENSP00000387640.2
IL23R	ENST00000473881.2	TSL:1	n.190+17113T>G	intron	N/A	ENSP00000486667.1

Frequencies

GnomAD3 genomes

AF:

0.0532

AC:

8089

AN:

152136

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0437

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0605

Gnomad ASJ

AF:

0.0960

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0450

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0623

Gnomad OTH

AF:

0.0574

GnomAD2 exomes

AF:

0.0443

AC:

11057

AN:

249390

AF XY:

0.0438

show subpopulations

Gnomad AFR exome

AF:

0.0445

Gnomad AMR exome

AF:

0.0420

Gnomad ASJ exome

AF:

0.0963

Gnomad EAS exome

AF:

0.000273

Gnomad FIN exome

AF:

0.0362

Gnomad NFE exome

AF:

0.0568

Gnomad OTH exome

AF:

0.0546

GnomAD4 exome

AF:

0.0539

AC:

61523

AN:

1142192

Hom.:

2009

Cov.:

AF XY:

0.0529

AC XY:

30850

AN XY:

583394

show subpopulations

African (AFR)

AF:

0.0423

AC:

1149

AN:

27154

American (AMR)

AF:

0.0422

AC:

1868

AN:

44308

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

2446

AN:

24176

East Asian (EAS)

AF:

0.0000785

AC:

AN:

38204

South Asian (SAS)

AF:

0.0131

AC:

1042

AN:

79812

European-Finnish (FIN)

AF:

0.0352

AC:

1868

AN:

53110

Middle Eastern (MID)

AF:

0.0814

AC:

418

AN:

5136

European-Non Finnish (NFE)

AF:

0.0609

AC:

49933

AN:

820418

Other (OTH)

AF:

0.0561

AC:

2796

AN:

49874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

2967

5934

8901

11868

14835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1666

3332

4998

6664

8330

<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:

0.0531

AC:

8092

AN:

152254

Hom.:

251

Cov.:

AF XY:

0.0518

AC XY:

3860

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0438

AC:

1819

AN:

41562

American (AMR)

AF:

0.0604

AC:

924

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0960

AC:

333

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5176

South Asian (SAS)

AF:

0.0131

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0450

AC:

478

AN:

10612

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0623

AC:

4234

AN:

68002

Other (OTH)

AF:

0.0568

AC:

120

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

384

767

1151

1534

1918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0594

Hom.:

1262

Bravo

AF:

0.0558

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.5

(source)

DANN

Benign

0.57

PhyloP100

-0.042

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over