rs1004819

Variant names:

• chr1-67204530-G-A
• rs1004819
• NM_144701.3:c.653-2380G>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.653-2380G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,990 control chromosomes in the GnomAD database, including 7,724 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 0.31 (7724 hom., cov: 32)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	NM_144701.3	c.653-2380G>A		intron_variant	Intron 5 of 10	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.653-2380G>A		intron_variant	Intron 5 of 10		XP_011539092.1
IL23R	XM_011540791.4	c.653-2380G>A		intron_variant	Intron 5 of 10		XP_011539093.1
IL23R	XM_047447227.1	c.653-2380G>A		intron_variant	Intron 5 of 10		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.653-2380G>A		intron_variant	Intron 5 of 10	1	NM_144701.3	ENSP00000321345.5

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46884 AN: 151872 Hom.: 7718 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.309 AC: 46909 AN: 151990 Hom.: 7724 Cov.: 32 AF XY: 0.311 AC XY: 23114 AN XY: 74300

Gnomad4 AFR AF: 0.297 AC: 0.296557 AN: 0.296557

Gnomad4 AMR AF: 0.246 AC: 0.246495 AN: 0.246495

Gnomad4 ASJ AF: 0.342 AC: 0.341878 AN: 0.341878

Gnomad4 EAS AF: 0.574 AC: 0.573916 AN: 0.573916

Gnomad4 SAS AF: 0.566 AC: 0.565948 AN: 0.565948

Gnomad4 FIN AF: 0.263 AC: 0.262829 AN: 0.262829

Gnomad4 NFE AF: 0.296 AC: 0.296004 AN: 0.296004

Gnomad4 OTH AF: 0.311 AC: 0.310721 AN: 0.310721

Alfa AF: 0.301 Hom.: 22155

Bravo AF: 0.302

Asia WGS AF: 0.500 AC: 1737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.41
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

Publications

LitVar

Other links and lift over

dbSNP: rs1004819; hg19: chr1-67670213;