rs6688383

Positions:

• chr1-67190271-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144701.3(IL23R):​c.491+7312A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,034 control chromosomes in the GnomAD database, including 6,999 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 0.30 (6999 hom., cov: 31)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL23R	NM_144701.3	c.491+7312A>G		intron_variant		ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.491+7312A>G		intron_variant			XP_011539092.1
IL23R	XM_011540791.4	c.491+7312A>G		intron_variant			XP_011539093.1
IL23R	XM_047447227.1	c.491+7312A>G		intron_variant			XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.491+7312A>G		intron_variant		1	NM_144701.3	ENSP00000321345	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44862 AN: 151916 Hom.: 6983 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.295 AC: 44917 AN: 152034 Hom.: 6999 Cov.: 31 AF XY: 0.298 AC XY: 22175 AN XY: 74302

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.313

Alfa AF: 0.311 Hom.: 7978

Bravo AF: 0.300

Asia WGS AF: 0.357 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs6688383; hg19: chr1-67655954;