rs12401432

Variant names:

• chr1-67191248-C-G
• rs12401432
• NM_144701.3:c.491+8289C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144701.3(IL23R):​c.491+8289C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,062 control chromosomes in the GnomAD database, including 6,899 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6899 hom., cov: 32)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 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.491+8289C>G		intron	N/A	NP_653302.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	ENST00000347310.10	TSL:1 MANE Select	c.491+8289C>G		intron	N/A	ENSP00000321345.5	Q5VWK5-1
	IL23R	ENST00000637002.1	TSL:1	n.491+8289C>G		intron	N/A	ENSP00000490340.2	A0A1B0GV19
	IL23R	ENST00000697164.1		c.491+8289C>G		intron	N/A	ENSP00000513153.1	A0A8V8TKS9

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44471 AN: 151944 Hom.: 6883 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.309

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44520 AN: 152062 Hom.: 6899 Cov.: 32 AF XY: 0.296 AC XY: 21984 AN XY: 74306

African (AFR) AF: 0.210 AC: 8718 AN: 41504

American (AMR) AF: 0.428 AC: 6533 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3472

East Asian (EAS) AF: 0.322 AC: 1668 AN: 5174

South Asian (SAS) AF: 0.287 AC: 1381 AN: 4820

European-Finnish (FIN) AF: 0.338 AC: 3572 AN: 10558

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 21067 AN: 67956

Other (OTH) AF: 0.312 AC: 658 AN: 2110

Alfa AF: 0.301 Hom.: 898

Bravo AF: 0.297

Asia WGS AF: 0.353 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.51
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12401432; hg19: chr1-67656931;