rs10489628

Variant names:

• chr1-67238424-G-A
• rs10489628
• NM_144701.3:c.1045+1622G>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.1045+1622G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,558 control chromosomes in the GnomAD database, including 14,319 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 0.43 (14319 hom., cov: 30)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 23 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	NM_144701.3	c.1045+1622G>A		intron_variant	Intron 8 of 10	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.1045+1622G>A		intron_variant	Intron 8 of 10		XP_011539092.1
IL23R	XM_011540791.4	c.1045+1622G>A		intron_variant	Intron 8 of 10		XP_011539093.1
IL23R	XM_047447227.1	c.1045+1622G>A		intron_variant	Intron 8 of 10		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.1045+1622G>A		intron_variant	Intron 8 of 10	1	NM_144701.3	ENSP00000321345.5

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64513 AN: 151448 Hom.: 14306 Cov.: 30

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.426 AC: 64572 AN: 151558 Hom.: 14319 Cov.: 30 AF XY: 0.422 AC XY: 31244 AN XY: 74024

African (AFR) AF: 0.527 AC: 21761 AN: 41272

American (AMR) AF: 0.479 AC: 7296 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1156 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1341 AN: 5152

South Asian (SAS) AF: 0.263 AC: 1258 AN: 4784

European-Finnish (FIN) AF: 0.369 AC: 3854 AN: 10444

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26677 AN: 67880

Other (OTH) AF: 0.397 AC: 839 AN: 2112

Alfa AF: 0.402 Hom.: 8223

Bravo AF: 0.440

Asia WGS AF: 0.335 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.56
DANN	Benign	0.59
PhyloP100		-1.2
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: rs10489628; hg19: chr1-67704107;