NM_005535.3:c.1619-516A>G

Variant names:

• chr19-18062793-T-C
• rs372889
• NM_005535.3:c.1619-516A>G

Variant summary

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

The NM_005535.3(IL12RB1):​c.1619-516A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,562 control chromosomes in the GnomAD database, including 18,463 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 0.49 (18463 hom., cov: 29)
• Consequence: IL12RB1 NM_005535.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 26 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB1	NM_005535.3	c.1619-516A>G		intron_variant	Intron 13 of 16	ENST00000593993.7	NP_005526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB1	ENST00000593993.7	c.1619-516A>G		intron_variant	Intron 13 of 16	1	NM_005535.3	ENSP00000472165.2
IL12RB1	ENST00000600835.6	c.1619-516A>G		intron_variant	Intron 14 of 17	1		ENSP00000470788.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74069 AN: 151444 Hom.: 18438 Cov.: 29

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.489 AC: 74119 AN: 151562 Hom.: 18463 Cov.: 29 AF XY: 0.487 AC XY: 36062 AN XY: 74006

African (AFR) AF: 0.511 AC: 21100 AN: 41312

American (AMR) AF: 0.371 AC: 5641 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1660 AN: 3464

East Asian (EAS) AF: 0.386 AC: 1982 AN: 5134

South Asian (SAS) AF: 0.338 AC: 1620 AN: 4798

European-Finnish (FIN) AF: 0.576 AC: 6048 AN: 10496

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34552 AN: 67860

Other (OTH) AF: 0.476 AC: 1001 AN: 2102

Alfa AF: 0.498 Hom.: 78259

Bravo AF: 0.475

Asia WGS AF: 0.399 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.23
DANN	Benign	0.25
PhyloP100		-2.0
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: rs372889; hg19: chr19-18173603;