rs4655686

Variant names:

• chr1-67172321-T-A
• rs4655686
• NM_144701.3:c.367+2683T>A

Variant summary

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

The NM_144701.3(IL23R):​c.367+2683T>A 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 152,076 control chromosomes in the GnomAD database, including 6,662 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 0.28 (6662 hom., cov: 32)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	NM_144701.3	c.367+2683T>A		intron_variant	Intron 3 of 10	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.367+2683T>A		intron_variant	Intron 3 of 10		XP_011539092.1
IL23R	XM_011540791.4	c.367+2683T>A		intron_variant	Intron 3 of 10		XP_011539093.1
IL23R	XM_047447227.1	c.367+2683T>A		intron_variant	Intron 3 of 10		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.367+2683T>A		intron_variant	Intron 3 of 10	1	NM_144701.3	ENSP00000321345.5

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43276 AN: 151958 Hom.: 6648 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.285 AC: 43320 AN: 152076 Hom.: 6662 Cov.: 32 AF XY: 0.288 AC XY: 21426 AN XY: 74324

African (AFR) AF: 0.182 AC: 7567 AN: 41488

American (AMR) AF: 0.427 AC: 6522 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3472

East Asian (EAS) AF: 0.321 AC: 1664 AN: 5182

South Asian (SAS) AF: 0.286 AC: 1381 AN: 4822

European-Finnish (FIN) AF: 0.337 AC: 3555 AN: 10552

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21059 AN: 67974

Other (OTH) AF: 0.307 AC: 648 AN: 2112

Alfa AF: 0.297 Hom.: 881

Bravo AF: 0.289

Asia WGS AF: 0.351 AC: 1220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.7
DANN	Benign	0.52
PhyloP100		-0.40
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: rs4655686; hg19: chr1-67638004;