rs8109496

Variant names:

• chr19-18079534-C-G
• rs8109496
• NM_005535.3:c.409+1298G>C

Variant summary

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

The NM_005535.3(IL12RB1):​c.409+1298G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,116 control chromosomes in the GnomAD database, including 2,398 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 0.17 (2398 hom., cov: 31)
• Consequence: IL12RB1 NM_005535.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB1	NM_005535.3	c.409+1298G>C		intron_variant	Intron 4 of 16	ENST00000593993.7	NP_005526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB1	ENST00000593993.7	c.409+1298G>C		intron_variant	Intron 4 of 16	1	NM_005535.3	ENSP00000472165.2
IL12RB1	ENST00000600835.6	c.409+1298G>C		intron_variant	Intron 5 of 17	1		ENSP00000470788.1
IL12RB1	ENST00000322153.11	c.409+1298G>C		intron_variant	Intron 4 of 9	1		ENSP00000314425.5

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26126 AN: 151998 Hom.: 2391 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.172 AC: 26159 AN: 152116 Hom.: 2398 Cov.: 31 AF XY: 0.171 AC XY: 12744 AN XY: 74374

African (AFR) AF: 0.135 AC: 5621 AN: 41506

American (AMR) AF: 0.119 AC: 1807 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3470

East Asian (EAS) AF: 0.0920 AC: 477 AN: 5182

South Asian (SAS) AF: 0.120 AC: 578 AN: 4822

European-Finnish (FIN) AF: 0.227 AC: 2408 AN: 10586

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14077 AN: 67998

Other (OTH) AF: 0.168 AC: 354 AN: 2108

Alfa AF: 0.199 Hom.: 366

Bravo AF: 0.161

Asia WGS AF: 0.115 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.54
PhyloP100		0.19
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: rs8109496; hg19: chr19-18190344;