1-67322008-A-T

Position:

• chr1-67322008-A-T

Variant summary

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

The NM_001374259.2(IL12RB2):​c.364+119A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 880,290 control chromosomes in the GnomAD database, including 11,931 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 (2073 hom., cov: 31)
  • Exomes 𝑓: 0.16 (9858 hom.)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

Genes affected

IL12RB2 (HGNC:5972): (interleukin 12 receptor subunit beta 2) The protein encoded by this gene is a type I transmembrane protein identified as a subunit of the interleukin 12 receptor complex. The coexpression of this and IL12RB1 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. The expression of this gene is up-regulated by interferon gamma in Th1 cells, and plays a role in Th1 cell differentiation. The up-regulation of this gene is found to be associated with a number of infectious diseases, such as Crohn's disease and leprosy, which is thought to contribute to the inflammatory response and host defense. Several transcript variants encoding different isoforms and non-protein coding transcripts have been found for this gene. [provided by RefSeq, Apr 2012]

IL12RB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL12RB2	NM_001374259.2	c.364+119A>T		intron_variant		ENST00000674203.2	NP_001361188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL12RB2	ENST00000674203.2	c.364+119A>T		intron_variant			NM_001374259.2	ENSP00000501329.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24659 AN: 151914 Hom.: 2067 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0579

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.155 AC: 113013 AN: 728258 Hom.: 9858 AF XY: 0.155 AC XY: 60422 AN XY: 389720

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.304

Gnomad4 EAS exome AF: 0.0377

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0855

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.162 AC: 24694 AN: 152032 Hom.: 2073 Cov.: 31 AF XY: 0.158 AC XY: 11707 AN XY: 74316

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.0577

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0802

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.181

Alfa AF: 0.0718 Hom.: 110

Bravo AF: 0.171

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs17129778; hg19: chr1-67787691;