dbSNP rs7530511: IL23R:p.Leu310Gln (chr1-67219704-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144701.3(IL23R):c.929T>A(p.Leu310Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L310P) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL23R
NM_144701.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.37

Publications

117 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12113279).

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.929T>A	p.Leu310Gln	missense	Exon 7 of 11	NP_653302.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IL23R	ENST00000347310.10	TSL:1 MANE Select	c.929T>A	p.Leu310Gln	missense	Exon 7 of 11	ENSP00000321345.5
IL23R	ENST00000425614.3	TSL:1	c.164T>A	p.Leu55Gln	missense	Exon 2 of 6	ENSP00000387640.2
IL23R	ENST00000473881.2	TSL:1	n.164T>A		non_coding_transcript_exon	Exon 2 of 4	ENSP00000486667.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461618

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727136

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111768

Other (OTH)

AF:

0.00

AC:

AN:

60390

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

218510

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.077

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.33

M_CAP

Benign

0.014

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

2.4

PrimateAI

Benign

0.34

PROVEAN

Benign

1.4

REVEL

Benign

0.13

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.011

Polyphen

0.091

Vest4

0.19

MutPred

0.50

Loss of stability (P = 0.0132)

MVP

0.64

MPC

0.18

ClinPred

0.33

GERP RS

4.9

PromoterAI

-0.0068

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.30

Mutation Taster

=97/3

polymorphism

(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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over