rs6695348

Variant names:

• chr1-67361333-T-C
• rs6695348
• NM_001374259.2:c.1259-6492T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001374259.2(IL12RB2):​c.1259-6492T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,090 control chromosomes in the GnomAD database, including 33,060 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 0.62 (33060 hom., cov: 32)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB2	NM_001374259.2	c.1259-6492T>C		intron_variant	Intron 10 of 16	ENST00000674203.2	NP_001361188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB2	ENST00000674203.2	c.1259-6492T>C		intron_variant	Intron 10 of 16		NM_001374259.2	ENSP00000501329.1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94583 AN: 151972 Hom.: 33062 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.629

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.622 AC: 94592 AN: 152090 Hom.: 33060 Cov.: 32 AF XY: 0.631 AC XY: 46891 AN XY: 74338

African (AFR) AF: 0.282 AC: 11669 AN: 41436

American (AMR) AF: 0.667 AC: 10199 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2108 AN: 3470

East Asian (EAS) AF: 0.733 AC: 3792 AN: 5170

South Asian (SAS) AF: 0.783 AC: 3774 AN: 4822

European-Finnish (FIN) AF: 0.867 AC: 9178 AN: 10584

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51620 AN: 68002

Other (OTH) AF: 0.626 AC: 1321 AN: 2110

Alfa AF: 0.679 Hom.: 4722

Bravo AF: 0.588

Asia WGS AF: 0.675 AC: 2346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.83
PhyloP100		0.21
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: rs6695348; hg19: chr1-67827016;