19-18059870-G-A

Variant names:

• chr19-18059870-G-A
• rs17882555
• NM_005535.3:c.1983+24C>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+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,329,962 control chromosomes in the GnomAD database, including 101,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (7534 hom., cov: 31)
  • Exomes 𝑓: 0.40 (94286 hom.)
• Consequence: IL12RB1 NM_005535.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.41
• Publications: 11 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=-0.9).
• BP6: Variant 19-18059870-G-A is Benign according to our data. Variant chr19-18059870-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688417.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 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+24C>T		intron	N/A	NP_005526.1	P42701-1
	IL12RB1	NM_001290024.2		c.2103+24C>T		intron	N/A	NP_001276953.1
	IL12RB1	NM_001440424.1		c.2004+24C>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+24C>T		intron	N/A	ENSP00000472165.2	P42701-1
	IL12RB1	ENST00000600835.6	TSL:1	c.1983+24C>T		intron	N/A	ENSP00000470788.1	P42701-1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 42403 AN: 149568 Hom.: 7533 Cov.: 31

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.288

GnomAD2 exomes AF: 0.308 AC: 52467 AN: 170374 AF XY: 0.313

Gnomad AFR exome AF: 0.0682

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.344

Gnomad EAS exome AF: 0.112

Gnomad FIN exome AF: 0.462

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.329

GnomAD4 exome AF: 0.401 AC: 473059 AN: 1180292 Hom.: 94286 Cov.: 18 AF XY: 0.396 AC XY: 234546 AN XY: 592346

African (AFR) AF: 0.0748 AC: 1857 AN: 24828

American (AMR) AF: 0.204 AC: 7397 AN: 36206

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 8462 AN: 23560

East Asian (EAS) AF: 0.197 AC: 6730 AN: 34144

South Asian (SAS) AF: 0.250 AC: 18591 AN: 74450

European-Finnish (FIN) AF: 0.462 AC: 22290 AN: 48230

Middle Eastern (MID) AF: 0.370 AC: 1934 AN: 5222

European-Non Finnish (NFE) AF: 0.439 AC: 387473 AN: 883628

Other (OTH) AF: 0.366 AC: 18325 AN: 50024

GnomAD4 genome AF: 0.283 AC: 42401 AN: 149670 Hom.: 7534 Cov.: 31 AF XY: 0.285 AC XY: 20831 AN XY: 73036

African (AFR) AF: 0.0766 AC: 3093 AN: 40380

American (AMR) AF: 0.232 AC: 3477 AN: 14966

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1208 AN: 3458

East Asian (EAS) AF: 0.137 AC: 681 AN: 4984

South Asian (SAS) AF: 0.245 AC: 1143 AN: 4660

European-Finnish (FIN) AF: 0.481 AC: 4983 AN: 10366

Middle Eastern (MID) AF: 0.334 AC: 97 AN: 290

European-Non Finnish (NFE) AF: 0.397 AC: 26841 AN: 67568

Other (OTH) AF: 0.285 AC: 596 AN: 2090

Alfa AF: 0.332 Hom.: 1956

Bravo AF: 0.252

Asia WGS AF: 0.170 AC: 595 AN: 3478

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	-0.90
CADD	Benign	0.085
DANN	Benign	0.64
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs17882555; hg19: chr19-18170680; COSMIC: COSV74045540;