NM_005535.3:c.701-238G>A

Variant names:

• chr19-18073837-C-T
• rs447171
• NM_005535.3:c.701-238G>A

Variant summary

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

The NM_005535.3(IL12RB1):​c.701-238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,090 control chromosomes in the GnomAD database, including 6,480 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 0.29 (6480 hom., cov: 32)
• Consequence: IL12RB1 NM_005535.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 3 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB1	NM_005535.3	c.701-238G>A		intron_variant	Intron 7 of 16	ENST00000593993.7	NP_005526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB1	ENST00000593993.7	c.701-238G>A		intron_variant	Intron 7 of 16	1	NM_005535.3	ENSP00000472165.2
IL12RB1	ENST00000600835.6	c.701-238G>A		intron_variant	Intron 8 of 17	1		ENSP00000470788.1
IL12RB1	ENST00000322153.11	c.701-238G>A		intron_variant	Intron 7 of 9	1		ENSP00000314425.5

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43687 AN: 151972 Hom.: 6461 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.288 AC: 43742 AN: 152090 Hom.: 6480 Cov.: 32 AF XY: 0.288 AC XY: 21393 AN XY: 74364

African (AFR) AF: 0.240 AC: 9954 AN: 41496

American (AMR) AF: 0.218 AC: 3326 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1129 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1928 AN: 5178

South Asian (SAS) AF: 0.239 AC: 1154 AN: 4822

European-Finnish (FIN) AF: 0.338 AC: 3572 AN: 10580

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21768 AN: 67952

Other (OTH) AF: 0.289 AC: 611 AN: 2112

Alfa AF: 0.304 Hom.: 917

Bravo AF: 0.276

Asia WGS AF: 0.330 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.53
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs447171; hg19: chr19-18184647;