rs76418789

Positions:

• chr1-67182913-G-A

Variant summary

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

The ENST00000347310.10(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 ENST00000347310.10 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.26

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

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
IL23R	NM_144701.3	c.445G>A	p.Gly149Arg	missense_variant	4/11	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.445G>A	p.Gly149Arg	missense_variant	4/11		XP_011539092.1
IL23R	XM_011540791.4	c.445G>A	p.Gly149Arg	missense_variant	4/11		XP_011539093.1
IL23R	XM_047447227.1	c.445G>A	p.Gly149Arg	missense_variant	4/11		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.445G>A	p.Gly149Arg	missense_variant	4/11	1	NM_144701.3	ENSP00000321345	P1

Frequencies

GnomAD3 genomes AF: 0.00497 AC: 756 AN: 152126 Hom.: 9 Cov.: 33

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.: 31 AF XY: 0.00678 AC XY: 921 AN XY: 135860

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.: 33 AF XY: 0.00617 AC XY: 4489 AN XY: 727200

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.: 9 Cov.: 33 AF XY: 0.00472 AC XY: 351 AN XY: 74436

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.: 14

Bravo AF: 0.00478

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00407 AC: 35

ExAC AF: 0.00708 AC: 860

Asia WGS AF: 0.0210 AC: 75 AN: 3478

EpiCase AF: 0.00513

EpiControl AF: 0.00397

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.69	D
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0090	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-7.9	D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.48		Gain of MoRF binding (P = 0.0298);
MVP		0.86
MPC		0.76
ClinPred		0.050	T
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

Other links and lift over

dbSNP: rs76418789; hg19: chr1-67648596; COSMIC: COSV61374959;