rs1109918

Positions:

• chr1-67396799-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001374259.2(IL12RB2):​c.*710A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 152,628 control chromosomes in the GnomAD database, including 27 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 0.013 (27 hom., cov: 31)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: IL12RB2 NM_001374259.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0134 (2036/152260) while in subpopulation NFE AF= 0.0205 (1392/67992). AF 95% confidence interval is 0.0196. There are 27 homozygotes in gnomad4. There are 960 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL12RB2	NM_001374259.2	c.*710A>G		3_prime_UTR_variant	17/17	ENST00000674203.2	NP_001361188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL12RB2	ENST00000674203.2	c.*710A>G		3_prime_UTR_variant	17/17		NM_001374259.2	ENSP00000501329	P1

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2035 AN: 152142 Hom.: 27 Cov.: 31

Gnomad AFR AF: 0.00348

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.0128

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.0136 AC: 5 AN: 368 Hom.: 0 Cov.: 0 AF XY: 0.0156 AC XY: 3 AN XY: 192

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0282

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00510

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0134 AC: 2036 AN: 152260 Hom.: 27 Cov.: 31 AF XY: 0.0129 AC XY: 960 AN XY: 74454

Gnomad4 AFR AF: 0.00347

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.0128

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0197 Hom.: 16

Bravo AF: 0.0133

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.84
DANN	Benign	0.38

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: rs1109918; hg19: chr1-67862482;