1-67222666-T-C

Variant names:

• chr1-67222666-T-C
• rs10489629
• NM_144701.3:c.955+2936T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144701.3(IL23R):​c.955+2936T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,028 control chromosomes in the GnomAD database, including 17,751 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 0.48 (17751 hom., cov: 31)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 92 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144701.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	NM_144701.3	MANE Select	c.955+2936T>C		intron	N/A	NP_653302.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	ENST00000347310.10	TSL:1 MANE Select	c.955+2936T>C		intron	N/A	ENSP00000321345.5
	IL23R	ENST00000425614.3	TSL:1	c.190+2936T>C		intron	N/A	ENSP00000387640.2
	IL23R	ENST00000473881.2	TSL:1	n.190+2936T>C		intron	N/A	ENSP00000486667.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72296 AN: 151910 Hom.: 17738 Cov.: 31

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.476 AC: 72357 AN: 152028 Hom.: 17751 Cov.: 31 AF XY: 0.470 AC XY: 34942 AN XY: 74304

African (AFR) AF: 0.558 AC: 23134 AN: 41454

American (AMR) AF: 0.539 AC: 8236 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3466

East Asian (EAS) AF: 0.264 AC: 1366 AN: 5176

South Asian (SAS) AF: 0.277 AC: 1334 AN: 4824

European-Finnish (FIN) AF: 0.413 AC: 4365 AN: 10564

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30970 AN: 67968

Other (OTH) AF: 0.455 AC: 960 AN: 2110

Alfa AF: 0.464 Hom.: 53324

Bravo AF: 0.493

Asia WGS AF: 0.344 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.51
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10489629; hg19: chr1-67688349;