chr1-67228519-A-G

Variant names:

• chr1-67228519-A-G
• rs2201841
• NM_144701.3:c.956-8194A>G

Variant summary

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

The NM_144701.3(IL23R):​c.956-8194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,464 control chromosomes in the GnomAD database, including 7,312 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 (7312 hom., cov: 29)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 184 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 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.956-8194A>G		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.956-8194A>G		intron	N/A	ENSP00000321345.5
	IL23R	ENST00000425614.3	TSL:1	c.191-8194A>G		intron	N/A	ENSP00000387640.2
	IL23R	ENST00000473881.2	TSL:1	n.190+8789A>G		intron	N/A	ENSP00000486667.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43206 AN: 151346 Hom.: 7304 Cov.: 29

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.285 AC: 43236 AN: 151464 Hom.: 7312 Cov.: 29 AF XY: 0.292 AC XY: 21573 AN XY: 74000

African (AFR) AF: 0.164 AC: 6760 AN: 41308

American (AMR) AF: 0.266 AC: 4047 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1171 AN: 3464

East Asian (EAS) AF: 0.724 AC: 3722 AN: 5138

South Asian (SAS) AF: 0.587 AC: 2797 AN: 4768

European-Finnish (FIN) AF: 0.294 AC: 3070 AN: 10454

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20602 AN: 67830

Other (OTH) AF: 0.311 AC: 654 AN: 2104

Alfa AF: 0.308 Hom.: 32794

Bravo AF: 0.275

Asia WGS AF: 0.579 AC: 2007 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.78
PhyloP100		0.35
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: rs2201841; hg19: chr1-67694202;