1-67196939-A-C

Position:

• chr1-67196939-A-C

Variant summary

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

The NM_144701.3(IL23R):​c.492-3798A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,072 control chromosomes in the GnomAD database, including 13,139 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 0.41 (13139 hom., cov: 32)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL23R	NM_144701.3	c.492-3798A>C		intron_variant		ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.492-3798A>C		intron_variant			XP_011539092.1
IL23R	XM_011540791.4	c.492-3798A>C		intron_variant			XP_011539093.1
IL23R	XM_047447227.1	c.492-3798A>C		intron_variant			XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.492-3798A>C		intron_variant		1	NM_144701.3	ENSP00000321345.5

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62633 AN: 151952 Hom.: 13104 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.412 AC: 62715 AN: 152072 Hom.: 13139 Cov.: 32 AF XY: 0.414 AC XY: 30767 AN XY: 74362

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.405

Alfa AF: 0.405 Hom.: 25881

Bravo AF: 0.423

Asia WGS AF: 0.432 AC: 1501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.43

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: rs10489630; hg19: chr1-67662622;