rs2064689

chr1-67187327-G-A

Variant summary

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

The NM_144701.3(IL23R):c.491+4368G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,018 control chromosomes in the GnomAD database, including 6,908 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 0.29 (6908 hom., cov: 33)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL23R	NM_144701.3	c.491+4368G>A		intron_variant		ENST00000347310.10
IL23R	XM_011540790.4	c.491+4368G>A		intron_variant
IL23R	XM_011540791.4	c.491+4368G>A		intron_variant
IL23R	XM_047447227.1	c.491+4368G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL23R	ENST00000347310.10	c.491+4368G>A		intron_variant		1	NM_144701.3	P1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44479 AN: 151900 Hom.: 6892 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.293 AC: 44529 AN: 152018 Hom.: 6908 Cov.: 33 AF XY: 0.296 AC XY: 22001 AN XY: 74286

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.311

Alfa AF: 0.303 Hom.: 14358

Bravo AF: 0.297

Asia WGS AF: 0.355 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.9
Dann	Benign	0.82

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: rs2064689; hg19: chr1-67653010;