NM_005535.3:c.1792-67G>A

Variant names:

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

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.1792-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 840,986 control chromosomes in the GnomAD database, including 54,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (7478 hom., cov: 31)
  • Exomes 𝑓: 0.36 (46910 hom.)
• Consequence: IL12RB1 NM_005535.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 19-18060152-C-T is Benign according to our data. Variant chr19-18060152-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42453 AN: 151906 Hom.: 7477 Cov.: 31

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.359 AC: 247378 AN: 688962 Hom.: 46910 AF XY: 0.356 AC XY: 128158 AN XY: 359634

African (AFR) AF: 0.0765 AC: 1376 AN: 17998

American (AMR) AF: 0.207 AC: 6606 AN: 31968

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 6164 AN: 17716

East Asian (EAS) AF: 0.191 AC: 6447 AN: 33768

South Asian (SAS) AF: 0.241 AC: 14332 AN: 59574

European-Finnish (FIN) AF: 0.453 AC: 21566 AN: 47630

Middle Eastern (MID) AF: 0.355 AC: 1408 AN: 3962

European-Non Finnish (NFE) AF: 0.402 AC: 177907 AN: 442296

Other (OTH) AF: 0.340 AC: 11572 AN: 34050

GnomAD4 genome AF: 0.279 AC: 42451 AN: 152024 Hom.: 7478 Cov.: 31 AF XY: 0.281 AC XY: 20877 AN XY: 74336

African (AFR) AF: 0.0780 AC: 3238 AN: 41502

American (AMR) AF: 0.227 AC: 3463 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1209 AN: 3466

East Asian (EAS) AF: 0.133 AC: 688 AN: 5168

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4816

European-Finnish (FIN) AF: 0.471 AC: 4974 AN: 10570

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

European-Non Finnish (NFE) AF: 0.394 AC: 26768 AN: 67932

Other (OTH) AF: 0.283 AC: 598 AN: 2112

Alfa AF: 0.358 Hom.: 15584

Bravo AF: 0.253

Asia WGS AF: 0.169 AC: 593 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 49% of patients studied by a panel of primary immunodeficiencies. Number of patients: 43. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.47
PhyloP100		-3.3
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: rs1870063; hg19: chr19-18170962; COSMIC: COSV107553440;