XM_047447227.1:c.1239+4494T>C

Variant names:

• chr1-67260421-T-C
• rs9988642
• XM_047447227.1:c.1239+4494T>C

Variant summary

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

The XM_047447227.1(IL23R):​c.1239+4494T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,112 control chromosomes in the GnomAD database, including 1,963 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 0.13 (1963 hom., cov: 31)
• Consequence: IL23R XM_047447227.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 39 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	XM_047447227.1	c.1239+4494T>C		intron_variant	Intron 10 of 10		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19364 AN: 151994 Hom.: 1960 Cov.: 31

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0313

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.127 AC: 19388 AN: 152112 Hom.: 1963 Cov.: 31 AF XY: 0.124 AC XY: 9218 AN XY: 74362

African (AFR) AF: 0.284 AC: 11781 AN: 41460

American (AMR) AF: 0.0878 AC: 1341 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 332 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0311 AC: 150 AN: 4820

European-Finnish (FIN) AF: 0.0603 AC: 638 AN: 10586

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0700 AC: 4759 AN: 68004

Other (OTH) AF: 0.108 AC: 229 AN: 2116

Alfa AF: 0.0942 Hom.: 2078

Bravo AF: 0.137

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.51
PhyloP100		-0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9988642; hg19: chr1-67726104;