rs11209026

Variant names:

• chr1-67240275-G-A
• rs11209026
• NM_144701.3:c.1142G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-67240275-G-A
• chr1-67240275-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XM_011540791.4(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. 12/21 in silico tools predict 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 XM_011540791.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.74
• Publications: 606 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000347310.10. 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.1142G>A	p.Arg381Gln	missense	Exon 9 of 11	NP_653302.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	ENST00000347310.10	TSL:1 MANE Select	c.1142G>A	p.Arg381Gln	missense	Exon 9 of 11	ENSP00000321345.5	Q5VWK5-1
	IL23R	ENST00000425614.3	TSL:1	c.377G>A	p.Arg126Gln	missense	Exon 4 of 6	ENSP00000387640.2	Q5VWK5-6
	IL23R	ENST00000637002.1	TSL:1	n.*603G>A		non_coding_transcript_exon	Exon 9 of 11	ENSP00000490340.2	A0A1B0GV19

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

GnomAD2 exomes AF: 0.0422 AC: 10589 AN: 250900 AF XY: 0.0426

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 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

African (AFR) AF: 0.0102 AC: 339 AN: 33348

American (AMR) AF: 0.0360 AC: 1610 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0716 AC: 1866 AN: 26052

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39616

South Asian (SAS) AF: 0.0145 AC: 1247 AN: 86064

European-Finnish (FIN) AF: 0.0482 AC: 2565 AN: 53170

Middle Eastern (MID) AF: 0.0514 AC: 291 AN: 5658

European-Non Finnish (NFE) AF: 0.0635 AC: 70095 AN: 1103968

Other (OTH) AF: 0.0495 AC: 2973 AN: 60070

GnomAD4 genome AF: 0.0458 AC: 6970 AN: 152162 Hom.: 217 Cov.: 33 AF XY: 0.0450 AC XY: 3350 AN XY: 74384

African (AFR) AF: 0.0125 AC: 519 AN: 41494

American (AMR) AF: 0.0509 AC: 779 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0711 AC: 247 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4820

European-Finnish (FIN) AF: 0.0599 AC: 633 AN: 10574

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0664 AC: 4519 AN: 68008

Other (OTH) AF: 0.0468 AC: 99 AN: 2114

Alfa AF: 0.0587 Hom.: 1484

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	-	Inflammatory bowel disease 17, protection against (1)
-	-	-	Psoriasis, protection against (1)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.24
MPC		0.59
ClinPred		0.033	T
GERP RS		5.2
Varity_R		0.35
gMVP		0.43
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

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