rs10889677

Positions:

• chr1-67259437-C-A
• chr1-67259437-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL23R	NM_144701.3	c.*309C>A		3_prime_UTR_variant	11/11	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.*309C>A		3_prime_UTR_variant	11/11		XP_011539092.1
IL23R	XM_011540791.4	c.*309C>A		3_prime_UTR_variant	11/11		XP_011539093.1
IL23R	XM_047447227.1	c.1239+3510C>A		intron_variant			XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.*309C>A		3_prime_UTR_variant	11/11	1	NM_144701.3	ENSP00000321345	P1
IL23R	ENST00000473881.2	c.*1025C>A		3_prime_UTR_variant, NMD_transcript_variant	4/4	1		ENSP00000486667

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

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.286

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.709

Gnomad4 SAS exome AF: 0.554

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.304

Gnomad4 OTH exome AF: 0.334

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

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.311

Alfa AF: 0.321 Hom.: 17493

Bravo AF: 0.274

Asia WGS AF: 0.579 AC: 2007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.4
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs10889677; hg19: chr1-67725120;