rs11086087

Variant names:

• chr19-18080854-C-G
• rs11086087
• NM_005535.3:c.387G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-18080854-C-G
• chr19-18080854-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005535.3(IL12RB1):​c.387G>C​(p.Val129Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,610,028 control chromosomes in the GnomAD database, including 10,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (940 hom., cov: 30)
  • Exomes 𝑓: 0.11 (9598 hom.)
• Consequence: IL12RB1 NM_005535.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.575
• 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: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-18080854-C-G is Benign according to our data. Variant chr19-18080854-C-G is described in ClinVar as Benign. ClinVar VariationId is 328599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.575 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 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.387G>C	p.Val129Val	synonymous	Exon 4 of 17	NP_005526.1	P42701-1
	IL12RB1	NM_001290024.2		c.507G>C	p.Val169Val	synonymous	Exon 5 of 18	NP_001276953.1
	IL12RB1	NM_001440424.1		c.387G>C	p.Val129Val	synonymous	Exon 4 of 17	NP_001427353.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB1	ENST00000593993.7	TSL:1 MANE Select	c.387G>C	p.Val129Val	synonymous	Exon 4 of 17	ENSP00000472165.2	P42701-1
	IL12RB1	ENST00000600835.6	TSL:1	c.387G>C	p.Val129Val	synonymous	Exon 5 of 18	ENSP00000470788.1	P42701-1
	IL12RB1	ENST00000322153.11	TSL:1	c.387G>C	p.Val129Val	synonymous	Exon 4 of 10	ENSP00000314425.5	P42701-3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15394 AN: 152024 Hom.: 938 Cov.: 30

Gnomad AFR AF: 0.0551

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.119 AC: 29807 AN: 251420 AF XY: 0.121

Gnomad AFR exome AF: 0.0534

Gnomad AMR exome AF: 0.0740

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.283

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.111 AC: 161735 AN: 1457886 Hom.: 9598 Cov.: 30 AF XY: 0.112 AC XY: 81006 AN XY: 725538

African (AFR) AF: 0.0508 AC: 1696 AN: 33410

American (AMR) AF: 0.0767 AC: 3429 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3511 AN: 26106

East Asian (EAS) AF: 0.236 AC: 9358 AN: 39672

South Asian (SAS) AF: 0.112 AC: 9682 AN: 86180

European-Finnish (FIN) AF: 0.107 AC: 5719 AN: 53382

Middle Eastern (MID) AF: 0.133 AC: 765 AN: 5754

European-Non Finnish (NFE) AF: 0.109 AC: 120462 AN: 1108412

Other (OTH) AF: 0.118 AC: 7113 AN: 60254

GnomAD4 genome AF: 0.101 AC: 15410 AN: 152142 Hom.: 940 Cov.: 30 AF XY: 0.103 AC XY: 7633 AN XY: 74372

African (AFR) AF: 0.0552 AC: 2291 AN: 41532

American (AMR) AF: 0.0939 AC: 1433 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3472

East Asian (EAS) AF: 0.279 AC: 1443 AN: 5166

South Asian (SAS) AF: 0.116 AC: 558 AN: 4812

European-Finnish (FIN) AF: 0.109 AC: 1152 AN: 10596

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7714 AN: 67988

Other (OTH) AF: 0.113 AC: 238 AN: 2106

Alfa AF: 0.113 Hom.: 332

Bravo AF: 0.0985

Asia WGS AF: 0.209 AC: 725 AN: 3478

EpiCase AF: 0.122

EpiControl AF: 0.125

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency (3)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.48
PhyloP100		-0.57
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: rs11086087; hg19: chr19-18191664; COSMIC: COSV59096426; COSMIC: COSV59096426;