ENST00000600835.6:c.-109-3524G>A

Variant names:

• chr19-18090456-C-T
• rs374326
• ENST00000600835.6:c.-109-3524G>A

Variant summary

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

The ENST00000600835.6(IL12RB1):​c.-109-3524G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,132 control chromosomes in the GnomAD database, including 44,609 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 0.76 (44609 hom., cov: 32)
• Consequence: IL12RB1 ENST00000600835.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 12 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: Orphanet, Labcorp Genetics (formerly Invitae)

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 = 0.916 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000600835.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB1	NM_001290024.2		c.12-3524G>A		intron	N/A	NP_001276953.1
	IL12RB1	NM_001440426.1		c.12-3524G>A		intron	N/A	NP_001427355.1
	IL12RB1	NM_001440427.1		c.12-3524G>A		intron	N/A	NP_001427356.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB1	ENST00000600835.6	TSL:1	c.-109-3524G>A		intron	N/A	ENSP00000470788.1	P42701-1
	IL12RB1	ENST00000598019.6	TSL:4	c.-110+194G>A		intron	N/A	ENSP00000468831.2	M0QX06
	IL12RB1	ENST00000594176.1	TSL:4	c.-110+194G>A		intron	N/A	ENSP00000473051.1	M0R382

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116090 AN: 152014 Hom.: 44561 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.764 AC: 116194 AN: 152132 Hom.: 44609 Cov.: 32 AF XY: 0.768 AC XY: 57101 AN XY: 74376

African (AFR) AF: 0.803 AC: 33327 AN: 41484

American (AMR) AF: 0.681 AC: 10422 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2751 AN: 3470

East Asian (EAS) AF: 0.938 AC: 4849 AN: 5170

South Asian (SAS) AF: 0.822 AC: 3963 AN: 4824

European-Finnish (FIN) AF: 0.787 AC: 8344 AN: 10596

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.737 AC: 50066 AN: 67976

Other (OTH) AF: 0.749 AC: 1582 AN: 2112

Alfa AF: 0.741 Hom.: 66367

Bravo AF: 0.753

Asia WGS AF: 0.872 AC: 3033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.32
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: rs374326; hg19: chr19-18201266;