dbSNP rs1004819: IL23R:c.653-2380G>A (chr1-67204530-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 classification points (ACMG Germline Pathogenicity v2019): 0P and 12B. BA1BP4_Strong

The NM_144701.3(IL23R):c.653-2380G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.309 (AC=46,909) in the gnomAD database across 151,990 control chromosomes, including 7,724 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.557. 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 0.31 ( 7724 hom., cov: 32)

Consequence

IL23R
NM_144701.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.372

Publications

127 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.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 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 = 0.5567 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_144701.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	NM_144701.3	MANE Select	c.653-2380G>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.653-2380G>A	intron	N/A	ENSP00000321345.5	Q5VWK5-1
IL23R	ENST00000637002.1	TSL:1	n.*114-2380G>A	intron	N/A	ENSP00000490340.2	A0A1B0GV19
IL23R	ENST00000697164.1		c.653-2380G>A	intron	N/A	ENSP00000513153.1	A0A8V8TKS9

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46884

AN:

151872

Hom.:

7718

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.574

Gnomad SAS

AF:

0.565

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.311

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

GnomAD4 genome

AF:

0.309

AC:

46909

AN:

151990

Hom.:

7724

Cov.:

AF XY:

0.311

AC XY:

23114

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.297

AC:

12284

AN:

41422

American (AMR)

AF:

0.246

AC:

3762

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1187

AN:

3472

East Asian (EAS)

AF:

0.574

AC:

2966

AN:

5168

South Asian (SAS)

AF:

0.566

AC:

2729

AN:

4822

European-Finnish (FIN)

AF:

0.263

AC:

2776

AN:

10562

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.296

AC:

20120

AN:

67972

Other (OTH)

AF:

0.311

AC:

655

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1633

3266

4899

6532

8165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

490

980

1470

1960

2450

<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:

0.301

Hom.:

22155

Bravo

AF:

0.302

Asia WGS

AF:

0.500

AC:

1737

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.551

AC:

67683

AN:

122808

Turkish Variome

AF:

0.439

AC:

679

AN:

1546

Hom.:

160

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.559

AC:

5013

AN:

8960

Hom.:

1417

ABraOM SABE-WGS-1171

AF:

0.290

AC:

679

AN:

2342

Hom.:

102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.1

(source)

DANN

Benign

0.41

PhyloP100

0.37

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