NM_144701.3:c.1046-136A>G

Variant names:

• chr1-67240043-A-G
• rs10889671
• NM_144701.3:c.1046-136A>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.1046-136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 703,526 control chromosomes in the GnomAD database, including 272,305 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 0.86 (55963 hom., cov: 33)
  • Exomes 𝑓: 0.88 (216342 hom.)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 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.1046-136A>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.1046-136A>G		intron	N/A	ENSP00000321345.5	Q5VWK5-1
	IL23R	ENST00000425614.3	TSL:1	c.281-136A>G		intron	N/A	ENSP00000387640.2	Q5VWK5-6
	IL23R	ENST00000473881.2	TSL:1	n.191-15794A>G		intron	N/A	ENSP00000486667.1	A0A0D9SFJ7

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130163 AN: 152104 Hom.: 55921 Cov.: 33

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.854

GnomAD4 exome AF: 0.885 AC: 487805 AN: 551304 Hom.: 216342 AF XY: 0.888 AC XY: 263571 AN XY: 296968

African (AFR) AF: 0.796 AC: 12079 AN: 15172

American (AMR) AF: 0.904 AC: 28788 AN: 31854

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 16974 AN: 18806

East Asian (EAS) AF: 0.987 AC: 31350 AN: 31750

South Asian (SAS) AF: 0.934 AC: 55230 AN: 59112

European-Finnish (FIN) AF: 0.836 AC: 28873 AN: 34524

Middle Eastern (MID) AF: 0.881 AC: 2233 AN: 2534

European-Non Finnish (NFE) AF: 0.873 AC: 286010 AN: 327666

Other (OTH) AF: 0.879 AC: 26268 AN: 29886

GnomAD4 genome AF: 0.856 AC: 130261 AN: 152222 Hom.: 55963 Cov.: 33 AF XY: 0.857 AC XY: 63764 AN XY: 74408

African (AFR) AF: 0.794 AC: 32975 AN: 41518

American (AMR) AF: 0.871 AC: 13327 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3149 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5122 AN: 5190

South Asian (SAS) AF: 0.937 AC: 4519 AN: 4822

European-Finnish (FIN) AF: 0.851 AC: 9008 AN: 10590

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.871 AC: 59258 AN: 68016

Other (OTH) AF: 0.855 AC: 1807 AN: 2114

Alfa AF: 0.861 Hom.: 10115

Bravo AF: 0.854

Asia WGS AF: 0.960 AC: 3341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.45
PhyloP100		0.083
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs10889671; hg19: chr1-67705726;