rs11209026

Positions:

• chr1-67240275-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.74

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]

ACMG classification

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	UniProt
IL23R	NM_144701.3	c.1142G>A	p.Arg381Gln	missense_variant	9/11	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.1142G>A	p.Arg381Gln	missense_variant	9/11		XP_011539092.1
IL23R	XM_011540791.4	c.1142G>A	p.Arg381Gln	missense_variant	9/11		XP_011539093.1
IL23R	XM_047447227.1	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	c.1142G>A	p.Arg381Gln	missense_variant	9/11	1	NM_144701.3	ENSP00000321345	P1

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6971 AN: 152044 Hom.: 217 Cov.: 33

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

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.: 28 AF XY: 0.0548 AC XY: 39655 AN XY: 723268

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.: 33 AF XY: 0.0450 AC XY: 3350 AN XY: 74384

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: 62

ESP6500EA AF: 0.0637 AC: 548

ExAC AF: 0.0415 AC: 5038

Asia WGS AF: 0.00982 AC: 34 AN: 3478

EpiCase AF: 0.0682

EpiControl AF: 0.0672

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.37	.;T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.88	D;D;D
MetaRNN	Benign	0.0026	T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.5	.;M;.
MutationTaster	Benign	0.56	D;D;N
PrimateAI	Benign	0.38	T
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	T
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

Other links and lift over

dbSNP: rs11209026; hg19: chr1-67705958; COSMIC: COSV61373825;