rs1884444

Variant names:

• chr1-67168129-G-T
• rs1884444
• NM_144701.3:c.9G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-67168129-G-T
• chr1-67168129-G-A

Variant summary

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

The NM_144701.3(IL23R):​c.9G>T​(p.Gln3His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,602,556 control chromosomes in the GnomAD database, including 228,378 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q3R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.52 (20363 hom., cov: 32)
  • Exomes 𝑓: 0.53 (208015 hom.)
• Consequence: IL23R NM_144701.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.735
• Publications: 120 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]

C1orf141 (HGNC:32044): (chromosome 1 open reading frame 141)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1682439E-5).
• BP6: Variant 1-67168129-G-T is Benign according to our data. Variant chr1-67168129-G-T is described in ClinVar as Benign. ClinVar VariationId is 1169496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

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.9G>T	p.Gln3His	missense	Exon 2 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.9G>T	p.Gln3His	missense	Exon 2 of 11	ENSP00000321345.5	Q5VWK5-1
	IL23R	ENST00000637002.1	TSL:1	n.9G>T		non_coding_transcript_exon	Exon 2 of 11	ENSP00000490340.2	A0A1B0GV19
	IL23R	ENST00000697164.1		c.9G>T	p.Gln3His	missense	Exon 1 of 9	ENSP00000513153.1	A0A8V8TKS9

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78178 AN: 151714 Hom.: 20359 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.478

GnomAD2 exomes AF: 0.524 AC: 131693 AN: 251106 AF XY: 0.535

Gnomad AFR exome AF: 0.494

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.596

Gnomad EAS exome AF: 0.644

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.532

Gnomad OTH exome AF: 0.510

GnomAD4 exome AF: 0.532 AC: 772277 AN: 1450724 Hom.: 208015 Cov.: 31 AF XY: 0.536 AC XY: 387377 AN XY: 722404

African (AFR) AF: 0.495 AC: 16471 AN: 33276

American (AMR) AF: 0.360 AC: 16105 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 15382 AN: 26058

East Asian (EAS) AF: 0.616 AC: 24365 AN: 39556

South Asian (SAS) AF: 0.629 AC: 54046 AN: 85958

European-Finnish (FIN) AF: 0.496 AC: 26432 AN: 53316

Middle Eastern (MID) AF: 0.523 AC: 3007 AN: 5748

European-Non Finnish (NFE) AF: 0.531 AC: 584738 AN: 1102114

Other (OTH) AF: 0.529 AC: 31731 AN: 59992

GnomAD4 genome AF: 0.515 AC: 78200 AN: 151832 Hom.: 20363 Cov.: 32 AF XY: 0.515 AC XY: 38211 AN XY: 74188

African (AFR) AF: 0.494 AC: 20449 AN: 41366

American (AMR) AF: 0.410 AC: 6256 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2115 AN: 3466

East Asian (EAS) AF: 0.641 AC: 3321 AN: 5180

South Asian (SAS) AF: 0.628 AC: 3020 AN: 4812

European-Finnish (FIN) AF: 0.512 AC: 5391 AN: 10520

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35894 AN: 67920

Other (OTH) AF: 0.477 AC: 1004 AN: 2106

Alfa AF: 0.526 Hom.: 69717

Bravo AF: 0.504

TwinsUK AF: 0.537 AC: 1993

ALSPAC AF: 0.516 AC: 1988

ESP6500AA AF: 0.500 AC: 2203

ESP6500EA AF: 0.528 AC: 4540

ExAC AF: 0.528 AC: 64158

Asia WGS AF: 0.563 AC: 1959 AN: 3474

EpiCase AF: 0.529

EpiControl AF: 0.525

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	10
DANN	Benign	0.95
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.000012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.73
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.13
Sift	Benign	0.38	T
Sift4G	Benign	0.34	T
Polyphen		0.0020	B
Vest4		0.14
MutPred		0.16		Loss of sheet (P = 0.1158)
MPC		0.60
ClinPred		0.0054	T
GERP RS		2.0
Varity_R		0.036
gMVP		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1884444; hg19: chr1-67633812; COSMIC: COSV61376571;