1-67236843-T-G

Position:

• chr1-67236843-T-G

Variant summary

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

The NM_144701.3(IL23R):​c.1045+41T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 1,294,446 control chromosomes in the GnomAD database, including 2,260 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 0.053 (251 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2009 hom.)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL23R	NM_144701.3	c.1045+41T>G		intron_variant		ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.1045+41T>G		intron_variant			XP_011539092.1
IL23R	XM_011540791.4	c.1045+41T>G		intron_variant			XP_011539093.1
IL23R	XM_047447227.1	c.1045+41T>G		intron_variant			XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.1045+41T>G		intron_variant		1	NM_144701.3	ENSP00000321345	P1

Frequencies

GnomAD3 genomes AF: 0.0532 AC: 8089 AN: 152136 Hom.: 251 Cov.: 32

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0605

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.0574

GnomAD3 exomes AF: 0.0443 AC: 11057 AN: 249390 Hom.: 316 AF XY: 0.0438 AC XY: 5909 AN XY: 134764

Gnomad AFR exome AF: 0.0445

Gnomad AMR exome AF: 0.0420

Gnomad ASJ exome AF: 0.0963

Gnomad EAS exome AF: 0.000273

Gnomad SAS exome AF: 0.0140

Gnomad FIN exome AF: 0.0362

Gnomad NFE exome AF: 0.0568

Gnomad OTH exome AF: 0.0546

GnomAD4 exome AF: 0.0539 AC: 61523 AN: 1142192 Hom.: 2009 Cov.: 16 AF XY: 0.0529 AC XY: 30850 AN XY: 583394

Gnomad4 AFR exome AF: 0.0423

Gnomad4 AMR exome AF: 0.0422

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.0000785

Gnomad4 SAS exome AF: 0.0131

Gnomad4 FIN exome AF: 0.0352

Gnomad4 NFE exome AF: 0.0609

Gnomad4 OTH exome AF: 0.0561

GnomAD4 genome AF: 0.0531 AC: 8092 AN: 152254 Hom.: 251 Cov.: 32 AF XY: 0.0518 AC XY: 3860 AN XY: 74446

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.0604

Gnomad4 ASJ AF: 0.0960

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0131

Gnomad4 FIN AF: 0.0450

Gnomad4 NFE AF: 0.0623

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0613 Hom.: 692

Bravo AF: 0.0558

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11465804; hg19: chr1-67702526;