chr1-67255184-T-C

Variant names:

• chr1-67255184-T-C
• rs6693831
• NM_144701.3:c.1149-653T>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.1149-653T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,106 control chromosomes in the GnomAD database, including 47,423 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 0.78 (47423 hom., cov: 31)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 17 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	NM_144701.3	MANE Select	c.1149-653T>C		intron	N/A	NP_653302.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	ENST00000347310.10	TSL:1 MANE Select	c.1149-653T>C		intron	N/A	ENSP00000321345.5
	IL23R	ENST00000425614.3	TSL:1	c.384-653T>C		intron	N/A	ENSP00000387640.2
	IL23R	ENST00000473881.2	TSL:1	n.191-653T>C		intron	N/A	ENSP00000486667.1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118858 AN: 151988 Hom.: 47371 Cov.: 31

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.782 AC: 118957 AN: 152106 Hom.: 47423 Cov.: 31 AF XY: 0.774 AC XY: 57511 AN XY: 74326

African (AFR) AF: 0.924 AC: 38368 AN: 41520

American (AMR) AF: 0.623 AC: 9517 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2700 AN: 3472

East Asian (EAS) AF: 0.779 AC: 4028 AN: 5168

South Asian (SAS) AF: 0.808 AC: 3895 AN: 4818

European-Finnish (FIN) AF: 0.633 AC: 6664 AN: 10534

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51121 AN: 67996

Other (OTH) AF: 0.764 AC: 1616 AN: 2114

Alfa AF: 0.762 Hom.: 186653

Bravo AF: 0.785

Asia WGS AF: 0.795 AC: 2766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.9
DANN	Benign	0.31
PhyloP100		0.023
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: rs6693831; hg19: chr1-67720867;