rs12070470

Variant names:

• chr1-67231588-T-C
• rs12070470
• NM_144701.3:c.956-5125T>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.956-5125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0893 in 152,180 control chromosomes in the GnomAD database, including 717 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 0.089 (717 hom., cov: 32)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 10 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 (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	NM_144701.3	c.956-5125T>C		intron_variant	Intron 7 of 10	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.956-5125T>C		intron_variant	Intron 7 of 10		XP_011539092.1
IL23R	XM_011540791.4	c.956-5125T>C		intron_variant	Intron 7 of 10		XP_011539093.1
IL23R	XM_047447227.1	c.956-5125T>C		intron_variant	Intron 7 of 10		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.956-5125T>C		intron_variant	Intron 7 of 10	1	NM_144701.3	ENSP00000321345.5

Frequencies

GnomAD3 genomes AF: 0.0894 AC: 13592 AN: 152062 Hom.: 717 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0651

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0703

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0866

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

GnomAD4 genome AF: 0.0893 AC: 13592 AN: 152180 Hom.: 717 Cov.: 32 AF XY: 0.0902 AC XY: 6711 AN XY: 74410

African (AFR) AF: 0.0565 AC: 2347 AN: 41544

American (AMR) AF: 0.0650 AC: 994 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0702 AC: 338 AN: 4816

European-Finnish (FIN) AF: 0.147 AC: 1555 AN: 10564

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7535 AN: 68002

Other (OTH) AF: 0.0857 AC: 181 AN: 2112

Alfa AF: 0.103 Hom.: 1396

Bravo AF: 0.0814

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-1.2
PromoterAI		0.0070	Neutral
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: rs12070470; hg19: chr1-67697271;