1-67240043-A-G

Variant names:

• chr1-67240043-A-G
• rs10889671
• NM_144701.3:c.1046-136A>G

Variant summary

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

The NM_144701.3(IL23R):​c.1046-136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 703,526 control chromosomes in the GnomAD database, including 272,305 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 0.86 (55963 hom., cov: 33)
  • Exomes 𝑓: 0.88 (216342 hom.)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	NM_144701.3	c.1046-136A>G		intron_variant	Intron 8 of 10	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.1046-136A>G		intron_variant	Intron 8 of 10		XP_011539092.1
IL23R	XM_011540791.4	c.1046-136A>G		intron_variant	Intron 8 of 10		XP_011539093.1
IL23R	XM_047447227.1	c.1046-136A>G		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.1046-136A>G		intron_variant	Intron 8 of 10	1	NM_144701.3	ENSP00000321345.5

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130163 AN: 152104 Hom.: 55921 Cov.: 33

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.854

GnomAD4 exome AF: 0.885 AC: 487805 AN: 551304 Hom.: 216342 AF XY: 0.888 AC XY: 263571 AN XY: 296968

Gnomad4 AFR exome AF: 0.796

Gnomad4 AMR exome AF: 0.904

Gnomad4 ASJ exome AF: 0.903

Gnomad4 EAS exome AF: 0.987

Gnomad4 SAS exome AF: 0.934

Gnomad4 FIN exome AF: 0.836

Gnomad4 NFE exome AF: 0.873

Gnomad4 OTH exome AF: 0.879

GnomAD4 genome AF: 0.856 AC: 130261 AN: 152222 Hom.: 55963 Cov.: 33 AF XY: 0.857 AC XY: 63764 AN XY: 74408

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.871

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.937

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.871

Gnomad4 OTH AF: 0.855

Alfa AF: 0.864 Hom.: 9886

Bravo AF: 0.854

Asia WGS AF: 0.960 AC: 3341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs10889671; hg19: chr1-67705726;