chr1-67219433-C-T

Position:

• chr1-67219433-C-T

Variant summary

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

The NM_144701.3(IL23R):​c.799-141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 732,406 control chromosomes in the GnomAD database, including 290,068 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 (56972 hom., cov: 33)
  • Exomes 𝑓: 0.90 (233096 hom.)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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=-0.97).
• 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/exons	MANE	Protein	UniProt
IL23R	NM_144701.3	c.799-141C>T		intron_variant		ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.799-141C>T		intron_variant			XP_011539092.1
IL23R	XM_011540791.4	c.799-141C>T		intron_variant			XP_011539093.1
IL23R	XM_047447227.1	c.799-141C>T		intron_variant			XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.799-141C>T		intron_variant		1	NM_144701.3	ENSP00000321345.5

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131281 AN: 152124 Hom.: 56938 Cov.: 33

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.862

GnomAD4 exome AF: 0.895 AC: 519403 AN: 580164 Hom.: 233096 AF XY: 0.899 AC XY: 278833 AN XY: 310208

Gnomad4 AFR exome AF: 0.777

Gnomad4 AMR exome AF: 0.907

Gnomad4 ASJ exome AF: 0.918

Gnomad4 EAS exome AF: 0.988

Gnomad4 SAS exome AF: 0.966

Gnomad4 FIN exome AF: 0.837

Gnomad4 NFE exome AF: 0.885

Gnomad4 OTH exome AF: 0.891

GnomAD4 genome AF: 0.863 AC: 131371 AN: 152242 Hom.: 56972 Cov.: 33 AF XY: 0.864 AC XY: 64295 AN XY: 74440

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.970

Gnomad4 FIN AF: 0.854

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.863

Alfa AF: 0.888 Hom.: 79012

Bravo AF: 0.860

Asia WGS AF: 0.966 AC: 3359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.8
DANN	Benign	0.77

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: rs2863212; hg19: chr1-67685116;