rs12041056

Variant names:

• chr1-67161577-C-T
• rs12041056
• ENST00000637002.1:n.-29-6515C>T

Variant summary

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

The ENST00000637002.1(IL23R):​n.-29-6515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,334 control chromosomes in the GnomAD database, including 9,539 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 0.32 (9539 hom., cov: 31)
• Consequence: IL23R ENST00000637002.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	XM_011540790.4	c.-29-6515C>T		intron_variant	Intron 1 of 10		XP_011539092.1
IL23R	XM_011540791.4	c.-30+750C>T		intron_variant	Intron 1 of 10		XP_011539093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000637002.1	n.-29-6515C>T		intron_variant	Intron 1 of 10	1		ENSP00000490340.2
C1orf141	ENST00000371007.6	c.-103-30350G>A		intron_variant	Intron 1 of 7	5		ENSP00000360046.1
C1orf141	ENST00000448166.6	c.-103-30350G>A		intron_variant	Intron 1 of 9	5		ENSP00000415519.2
IL23R	ENST00000697222.1	c.-29-6515C>T		intron_variant	Intron 1 of 2			ENSP00000513189.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48116 AN: 151222 Hom.: 9542 Cov.: 31

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.318 AC: 48105 AN: 151334 Hom.: 9539 Cov.: 31 AF XY: 0.320 AC XY: 23636 AN XY: 73972

African (AFR) AF: 0.0785 AC: 3245 AN: 41352

American (AMR) AF: 0.307 AC: 4662 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1615 AN: 3466

East Asian (EAS) AF: 0.611 AC: 3160 AN: 5168

South Asian (SAS) AF: 0.525 AC: 2531 AN: 4818

European-Finnish (FIN) AF: 0.373 AC: 3807 AN: 10196

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.411 AC: 27888 AN: 67822

Other (OTH) AF: 0.314 AC: 659 AN: 2102

Alfa AF: 0.390 Hom.: 15836

Bravo AF: 0.301

Asia WGS AF: 0.487 AC: 1683 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.17
DANN	Benign	0.37
PhyloP100		-0.30
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: rs12041056; hg19: chr1-67627260;