chr19-18091302-G-T

Position:

• chr19-18091302-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000600835.6(IL12RB1):​c.-109-4370C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,222 control chromosomes in the GnomAD database, including 2,165 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 0.16 (2165 hom., cov: 31)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: IL12RB1 ENST00000600835.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12RB1	NM_001290024.1	c.12-4370C>A		intron_variant
IL12RB1	XM_006722741.4	c.12-4370C>A		intron_variant
IL12RB1	XM_011527966.3	c.12-4370C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB1	ENST00000600835.6	c.-109-4370C>A		intron_variant		1		P1
IL12RB1	ENST00000594176.1	c.-229-533C>A		intron_variant		4
IL12RB1	ENST00000598019.6	c.-230+142C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25050 AN: 152054 Hom.: 2163 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.120 AC: 6 AN: 50 Hom.: 0 AF XY: 0.125 AC XY: 5 AN XY: 40

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.0588

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.165 AC: 25065 AN: 152172 Hom.: 2165 Cov.: 31 AF XY: 0.165 AC XY: 12255 AN XY: 74376

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.164

Alfa AF: 0.0967 Hom.: 146

Bravo AF: 0.154

Asia WGS AF: 0.118 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs425648; hg19: chr19-18202112;