Variant rs76418789 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_144701.3(IL23R):c.445G>A(p.Gly149Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00616 in 1,614,028 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0063 ( 112 hom. )

Consequence

IL23R
NM_144701.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.26

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

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008963466).

BP6

Variant 1-67182913-G-A is Benign according to our data. Variant chr1-67182913-G-A is described in ClinVar as [Benign]. Clinvar id is 1167634.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IL23R	NM_144701.3 linkuse as main transcript	c.445G>A	p.Gly149Arg	missense_variant	4/11	ENST00000347310.10
IL23R	XM_011540790.4 linkuse as main transcript	c.445G>A	p.Gly149Arg	missense_variant	4/11
IL23R	XM_011540791.4 linkuse as main transcript	c.445G>A	p.Gly149Arg	missense_variant	4/11
IL23R	XM_047447227.1 linkuse as main transcript	c.445G>A	p.Gly149Arg	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL23R	ENST00000347310.10 linkuse as main transcript	c.445G>A	p.Gly149Arg	missense_variant	4/11	1	NM_144701.3	P1	Q5VWK5-1

Frequencies

GnomAD3 genomes

AF:

0.00497

AC:

756

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00341

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0444

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00520

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00728

AC:

1829

AN:

251362

Hom.:

AF XY:

0.00678

AC XY:

921

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00749

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0481

Gnomad SAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.00540

Gnomad NFE exome

AF:

0.00412

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00628

AC:

9182

AN:

1461784

Hom.:

112

Cov.:

AF XY:

0.00617

AC XY:

4489

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00608

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0628

Gnomad4 SAS exome

AF:

0.00286

Gnomad4 FIN exome

AF:

0.00528

Gnomad4 NFE exome

AF:

0.00489

Gnomad4 OTH exome

AF:

0.00686

GnomAD4 genome

AF:

0.00496

AC:

755

AN:

152244

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

351

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0444

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00660

Gnomad4 NFE

AF:

0.00521

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00599

Hom.:

Bravo

AF:

0.00478

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.00708

AC:

860

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.00513

EpiControl

AF:

0.00397

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Pathogenic

0.18

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Uncertain

0.69

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0090

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-7.9

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.92

MutPred

0.48

Gain of MoRF binding (P = 0.0298);

MVP

0.86

MPC

0.76

ClinPred

0.050

GERP RS

5.2

Varity_R

0.89

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over