19-18059847-C-A

Variant names:

• chr19-18059847-C-A
• rs12461312
• NM_005535.3:c.1983+47G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005535.3(IL12RB1):​c.1983+47G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,050,200 control chromosomes in the GnomAD database, including 78,950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (7505 hom., cov: 31)
  • Exomes 𝑓: 0.36 (71445 hom.)
• Consequence: IL12RB1 NM_005535.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11
• 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: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-18059847-C-A is Benign according to our data. Variant chr19-18059847-C-A is described in ClinVar as Benign. ClinVar VariationId is 2688418.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005535.3. 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_005535.3	MANE Select	c.1983+47G>T		intron	N/A	NP_005526.1	P42701-1
	IL12RB1	NM_001290024.2		c.2103+47G>T		intron	N/A	NP_001276953.1
	IL12RB1	NM_001440424.1		c.2004+47G>T		intron	N/A	NP_001427353.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB1	ENST00000593993.7	TSL:1 MANE Select	c.1983+47G>T		intron	N/A	ENSP00000472165.2	P42701-1
	IL12RB1	ENST00000600835.6	TSL:1	c.1983+47G>T		intron	N/A	ENSP00000470788.1	P42701-1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42171 AN: 151902 Hom.: 7505 Cov.: 31

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.286

GnomAD2 exomes AF: 0.305 AC: 48467 AN: 158674 AF XY: 0.310

Gnomad AFR exome AF: 0.0616

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.112

Gnomad FIN exome AF: 0.460

Gnomad NFE exome AF: 0.395

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.359 AC: 322080 AN: 898180 Hom.: 71445 Cov.: 12 AF XY: 0.356 AC XY: 164783 AN XY: 462414

African (AFR) AF: 0.0566 AC: 1288 AN: 22766

American (AMR) AF: 0.201 AC: 7102 AN: 35328

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 7559 AN: 22056

East Asian (EAS) AF: 0.190 AC: 6442 AN: 33840

South Asian (SAS) AF: 0.238 AC: 16632 AN: 69892

European-Finnish (FIN) AF: 0.454 AC: 21817 AN: 48072

Middle Eastern (MID) AF: 0.350 AC: 1645 AN: 4700

European-Non Finnish (NFE) AF: 0.397 AC: 245807 AN: 619928

Other (OTH) AF: 0.331 AC: 13788 AN: 41598

GnomAD4 genome AF: 0.277 AC: 42164 AN: 152020 Hom.: 7505 Cov.: 31 AF XY: 0.279 AC XY: 20709 AN XY: 74318

African (AFR) AF: 0.0692 AC: 2873 AN: 41504

American (AMR) AF: 0.227 AC: 3471 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1209 AN: 3468

East Asian (EAS) AF: 0.132 AC: 677 AN: 5140

South Asian (SAS) AF: 0.237 AC: 1147 AN: 4830

European-Finnish (FIN) AF: 0.471 AC: 4981 AN: 10572

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26831 AN: 67924

Other (OTH) AF: 0.282 AC: 595 AN: 2112

Alfa AF: 0.306 Hom.: 2743

Bravo AF: 0.250

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.77
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12461312; hg19: chr19-18170657; COSMIC: COSV74045548;