chr19-18060152-C-G

Variant names:

• chr19-18060152-C-G
• rs1870063
• NM_005535.3:c.1792-67G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005535.3(IL12RB1):​c.1792-67G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000725 in 690,112 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: IL12RB1 NM_005535.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28
• Publications: 21 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB1	NM_005535.3	c.1792-67G>C		intron_variant	Intron 15 of 16	ENST00000593993.7	NP_005526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB1	ENST00000593993.7	c.1792-67G>C		intron_variant	Intron 15 of 16	1	NM_005535.3	ENSP00000472165.2
IL12RB1	ENST00000600835.6	c.1792-67G>C		intron_variant	Intron 16 of 17	1		ENSP00000470788.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000725 AC: 5 AN: 690112 Hom.: 0 AF XY: 0.00000278 AC XY: 1 AN XY: 360230

African (AFR) AF: 0.00 AC: 0 AN: 18012

American (AMR) AF: 0.00 AC: 0 AN: 32004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17726

East Asian (EAS) AF: 0.00 AC: 0 AN: 33776

South Asian (SAS) AF: 0.00 AC: 0 AN: 59610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3970

European-Non Finnish (NFE) AF: 0.00000902 AC: 4 AN: 443236

Other (OTH) AF: 0.0000293 AC: 1 AN: 34106

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 15584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.066
DANN	Benign	0.51
PhyloP100		-3.3

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: rs1870063; hg19: chr19-18170962;