rs10889667

Positions:

• chr1-67189524-A-C
• chr1-67189524-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144701.3(IL23R):​c.491+6565A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,196 control chromosomes in the GnomAD database, including 59,335 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 0.88 (59335 hom., cov: 33)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440

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]

C1orf141 (HGNC:32044): (chromosome 1 open reading frame 141)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL23R	NM_144701.3	c.491+6565A>C		intron_variant		ENST00000347310.10
IL23R	XM_011540790.4	c.491+6565A>C		intron_variant
IL23R	XM_011540791.4	c.491+6565A>C		intron_variant
IL23R	XM_047447227.1	c.491+6565A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL23R	ENST00000347310.10	c.491+6565A>C		intron_variant		1	NM_144701.3	P1

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134223 AN: 152078 Hom.: 59292 Cov.: 33

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.883 AC: 134322 AN: 152196 Hom.: 59335 Cov.: 33 AF XY: 0.883 AC XY: 65671 AN XY: 74404

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.887

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.858

Alfa AF: 0.874 Hom.: 7203

Bravo AF: 0.883

Asia WGS AF: 0.966 AC: 3359 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.0
DANN	Benign	0.78

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: rs10889667; hg19: chr1-67655207;