19-18091302-G-T

Variant names:

• chr19-18091302-G-T
• rs425648
• ENST00000600835.6:c.-109-4370C>A

Variant summary

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

The NM_001290024.2(IL12RB1):​c.12-4370C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,222 control chromosomes in the GnomAD database, including 2,165 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 0.16 (2165 hom., cov: 31)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: IL12RB1 NM_001290024.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290024.2. 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.12-4370C>A		intron	N/A	NP_001276953.1
	IL12RB1	NM_001440426.1		c.12-4370C>A		intron	N/A	NP_001427355.1
	IL12RB1	NM_001440427.1		c.12-4370C>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.-109-4370C>A		intron	N/A	ENSP00000470788.1	P42701-1
	IL12RB1	ENST00000598019.6	TSL:4	c.-230+142C>A		intron	N/A	ENSP00000468831.2	M0QX06
	IL12RB1	ENST00000594176.1	TSL:4	c.-229-533C>A		intron	N/A	ENSP00000473051.1	M0R382

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25050 AN: 152054 Hom.: 2163 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.120 AC: 6 AN: 50 Hom.: 0 AF XY: 0.125 AC XY: 5 AN XY: 40

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.0588 AC: 2 AN: 34

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.165 AC: 25065 AN: 152172 Hom.: 2165 Cov.: 31 AF XY: 0.165 AC XY: 12255 AN XY: 74376

African (AFR) AF: 0.124 AC: 5139 AN: 41522

American (AMR) AF: 0.129 AC: 1974 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3472

East Asian (EAS) AF: 0.102 AC: 527 AN: 5174

South Asian (SAS) AF: 0.124 AC: 599 AN: 4812

European-Finnish (FIN) AF: 0.216 AC: 2290 AN: 10596

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13384 AN: 67988

Other (OTH) AF: 0.164 AC: 346 AN: 2114

Alfa AF: 0.0980 Hom.: 155

Bravo AF: 0.154

Asia WGS AF: 0.118 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.76
PhyloP100		0.43
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: rs425648; hg19: chr19-18202112;