Variant 1-67240275-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144701.3(IL23R):c.1142G>A(p.Arg381Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0548 in 1,604,812 control chromosomes in the GnomAD database, including 2,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 217 hom., cov: 33)

Exomes 𝑓: 0.056 ( 2622 hom. )

Consequence

IL23R
NM_144701.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.74

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025800169).

BP6

Variant 1-67240275-G-A is Benign according to our data. Variant chr1-67240275-G-A is described in ClinVar as [Benign]. Clinvar id is 3108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IL23R	NM_144701.3 linkuse as main transcript	c.1142G>A	p.Arg381Gln	missense_variant	9/11	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4 linkuse as main transcript	c.1142G>A	p.Arg381Gln	missense_variant	9/11		XP_011539092.1
IL23R	XM_011540791.4 linkuse as main transcript	c.1142G>A	p.Arg381Gln	missense_variant	9/11		XP_011539093.1
IL23R	XM_047447227.1 linkuse as main transcript	c.1142G>A	p.Arg381Gln	missense_variant	9/11		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10 linkuse as main transcript	c.1142G>A	p.Arg381Gln	missense_variant	9/11	1	NM_144701.3	ENSP00000321345	P1	Q5VWK5-1

Frequencies

GnomAD3 genomes

AF:

0.0458

AC:

6971

AN:

152044

Hom.:

217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0510

Gnomad ASJ

AF:

0.0711

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.0599

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0665

Gnomad OTH

AF:

0.0473

GnomAD3 exomes

AF:

0.0422

AC:

10589

AN:

250900

Hom.:

306

AF XY:

0.0426

AC XY:

5771

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.0359

Gnomad ASJ exome

AF:

0.0687

Gnomad EAS exome

AF:

0.000327

Gnomad SAS exome

AF:

0.0151

Gnomad FIN exome

AF:

0.0500

Gnomad NFE exome

AF:

0.0586

Gnomad OTH exome

AF:

0.0456

GnomAD4 exome

AF:

0.0558

AC:

80990

AN:

1452650

Hom.:

2622

Cov.:

AF XY:

0.0548

AC XY:

39655

AN XY:

723268

show subpopulations

Gnomad4 AFR exome

AF:

0.0102

Gnomad4 AMR exome

AF:

0.0360

Gnomad4 ASJ exome

AF:

0.0716

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0145

Gnomad4 FIN exome

AF:

0.0482

Gnomad4 NFE exome

AF:

0.0635

Gnomad4 OTH exome

AF:

0.0495

GnomAD4 genome

AF:

0.0458

AC:

6970

AN:

152162

Hom.:

217

Cov.:

AF XY:

0.0450

AC XY:

3350

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0125

Gnomad4 AMR

AF:

0.0509

Gnomad4 ASJ

AF:

0.0711

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0137

Gnomad4 FIN

AF:

0.0599

Gnomad4 NFE

AF:

0.0664

Gnomad4 OTH

AF:

0.0468

Alfa

AF:

0.0610

Hom.:

812

Bravo

AF:

0.0450

TwinsUK

AF:

0.0631

AC:

234

ALSPAC

AF:

0.0706

AC:

272

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.0637

AC:

548

ExAC

AF:

0.0415

AC:

5038

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.0682

EpiControl

AF:

0.0672

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Inflammatory bowel disease 17, protection against

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Apr 01, 2010

- -

Psoriasis, protection against

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Apr 01, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

.;T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.88

D;D;D

MetaRNN

Benign

0.0026

T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.5

.;M;.

MutationTaster

Benign

0.56

D;D;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.2

.;N;.

REVEL

Benign

0.18

Sift

Pathogenic

0.0

.;D;.

Sift4G

Pathogenic

0.0

.;D;D

Polyphen

1.0

.;D;D

Vest4

0.24, 0.17

MPC

0.59

ClinPred

0.033

GERP RS

5.2

Varity_R

0.35

gMVP

0.43

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

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