1-67233571-T-C

Variant names:

• chr1-67233571-T-C
• rs11804284
• NM_144701.3:c.956-3142T>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.956-3142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,140 control chromosomes in the GnomAD database, including 55,505 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 0.85 (55505 hom., cov: 31)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• Publications: 8 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 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.956-3142T>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.956-3142T>C		intron	N/A	ENSP00000321345.5
	IL23R	ENST00000425614.3	TSL:1	c.191-3142T>C		intron	N/A	ENSP00000387640.2
	IL23R	ENST00000473881.2	TSL:1	n.190+13841T>C		intron	N/A	ENSP00000486667.1

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129567 AN: 152022 Hom.: 55469 Cov.: 31

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.852 AC: 129658 AN: 152140 Hom.: 55505 Cov.: 31 AF XY: 0.854 AC XY: 63501 AN XY: 74364

African (AFR) AF: 0.782 AC: 32463 AN: 41490

American (AMR) AF: 0.871 AC: 13320 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 3135 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5110 AN: 5182

South Asian (SAS) AF: 0.936 AC: 4506 AN: 4816

European-Finnish (FIN) AF: 0.856 AC: 9046 AN: 10566

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.870 AC: 59187 AN: 68006

Other (OTH) AF: 0.850 AC: 1798 AN: 2116

Alfa AF: 0.873 Hom.: 27989

Bravo AF: 0.850

Asia WGS AF: 0.959 AC: 3335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.70
PhyloP100		0.10
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: rs11804284; hg19: chr1-67699254;