chr1-67259437-C-A

Variant names:

• chr1-67259437-C-A
• rs10889677
• NM_144701.3:c.*309C>A

Variant summary

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

The NM_144701.3(IL23R):​c.*309C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 360,760 control chromosomes in the GnomAD database, including 22,575 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 0.28 (7318 hom., cov: 32)
  • Exomes 𝑓: 0.36 (15257 hom.)
• Consequence: IL23R NM_144701.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 223 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	NM_144701.3	MANE Select	c.*309C>A		3_prime_UTR	Exon 11 of 11	NP_653302.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	ENST00000347310.10	TSL:1 MANE Select	c.*309C>A		3_prime_UTR	Exon 11 of 11	ENSP00000321345.5
	IL23R	ENST00000473881.2	TSL:1	n.*1025C>A		non_coding_transcript_exon	Exon 4 of 4	ENSP00000486667.1
	IL23R	ENST00000473881.2	TSL:1	n.*1025C>A		3_prime_UTR	Exon 4 of 4	ENSP00000486667.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43213 AN: 151888 Hom.: 7310 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.355 AC: 74117 AN: 208754 Hom.: 15257 Cov.: 0 AF XY: 0.373 AC XY: 41629 AN XY: 111556

African (AFR) AF: 0.155 AC: 987 AN: 6360

American (AMR) AF: 0.286 AC: 2148 AN: 7502

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 2070 AN: 5880

East Asian (EAS) AF: 0.709 AC: 7508 AN: 10588

South Asian (SAS) AF: 0.554 AC: 15608 AN: 28150

European-Finnish (FIN) AF: 0.272 AC: 2759 AN: 10160

Middle Eastern (MID) AF: 0.422 AC: 357 AN: 846

European-Non Finnish (NFE) AF: 0.304 AC: 38854 AN: 127828

Other (OTH) AF: 0.334 AC: 3826 AN: 11440

GnomAD4 genome AF: 0.284 AC: 43244 AN: 152006 Hom.: 7318 Cov.: 32 AF XY: 0.290 AC XY: 21570 AN XY: 74270

African (AFR) AF: 0.159 AC: 6605 AN: 41484

American (AMR) AF: 0.267 AC: 4071 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1195 AN: 3470

East Asian (EAS) AF: 0.724 AC: 3727 AN: 5148

South Asian (SAS) AF: 0.591 AC: 2836 AN: 4802

European-Finnish (FIN) AF: 0.293 AC: 3096 AN: 10562

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.304 AC: 20646 AN: 67956

Other (OTH) AF: 0.311 AC: 657 AN: 2114

Alfa AF: 0.307 Hom.: 31801

Bravo AF: 0.274

Asia WGS AF: 0.579 AC: 2007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.4
DANN	Benign	0.89
PhyloP100		-0.21
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: rs10889677; hg19: chr1-67725120;