rs2045387

Variant names:

• chr19-18089776-G-T
• rs2045387
• ENST00000600835.6:c.-109-2844C>A

Variant summary

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

The ENST00000600835.6(IL12RB1):​c.-109-2844C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,260 control chromosomes in the GnomAD database, including 3,249 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 0.18 (3249 hom., cov: 33)
• Consequence: IL12RB1 ENST00000600835.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 4 publications found

Genes affected

IL12RB1 (HGNC:5971): (interleukin 12 receptor subunit beta 1) The protein encoded by this gene is a type I transmembrane protein that belongs to the hemopoietin receptor superfamily. This protein binds to interleukine 12 (IL12) with a low affinity, and is thought to be a part of IL12 receptor complex. This protein forms a disulfide-linked oligomer, which is required for its IL12 binding activity. The coexpression of this and IL12RB2 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. Mutations in this gene impair the development of interleukin-17-producing T lymphocytes and result in increased susceptibility to mycobacterial and Salmonella infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

IL12RB1 Gene-Disease associations (from GenCC):

• Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB1	NM_001290024.2	c.12-2844C>A		intron_variant	Intron 1 of 17		NP_001276953.1
IL12RB1	NM_001440426.1	c.12-2844C>A		intron_variant	Intron 1 of 10		NP_001427355.1
IL12RB1	NM_001440427.1	c.12-2844C>A		intron_variant	Intron 1 of 10		NP_001427356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB1	ENST00000600835.6	c.-109-2844C>A		intron_variant	Intron 1 of 17	1		ENSP00000470788.1
IL12RB1	ENST00000598019.6	c.-110+874C>A		intron_variant	Intron 3 of 5	4		ENSP00000468831.2
IL12RB1	ENST00000594176.1	c.-110+874C>A		intron_variant	Intron 2 of 4	4		ENSP00000473051.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27708 AN: 152142 Hom.: 3254 Cov.: 33

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0209

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.182 AC: 27694 AN: 152260 Hom.: 3249 Cov.: 33 AF XY: 0.183 AC XY: 13603 AN XY: 74454

African (AFR) AF: 0.0574 AC: 2386 AN: 41568

American (AMR) AF: 0.137 AC: 2100 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3466

East Asian (EAS) AF: 0.0210 AC: 109 AN: 5194

South Asian (SAS) AF: 0.270 AC: 1303 AN: 4826

European-Finnish (FIN) AF: 0.285 AC: 3019 AN: 10596

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17294 AN: 67986

Other (OTH) AF: 0.174 AC: 367 AN: 2114

Alfa AF: 0.240 Hom.: 1986

Bravo AF: 0.162

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.30
PhyloP100		0.018
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2045387; hg19: chr19-18200586;