1-67371475-C-T

Variant names:

• chr1-67371475-C-T
• rs10493423
• NM_001374259.2:c.1460-961C>T

Variant summary

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

The NM_001374259.2(IL12RB2):​c.1460-961C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 151,290 control chromosomes in the GnomAD database, including 845 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 0.075 (845 hom., cov: 32)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB2	NM_001374259.2	c.1460-961C>T		intron_variant	Intron 11 of 16	ENST00000674203.2	NP_001361188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB2	ENST00000674203.2	c.1460-961C>T		intron_variant	Intron 11 of 16		NM_001374259.2	ENSP00000501329.1

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11350 AN: 151196 Hom.: 838 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0967

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.0860

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0513

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0824

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

GnomAD4 genome AF: 0.0753 AC: 11390 AN: 151290 Hom.: 845 Cov.: 32 AF XY: 0.0767 AC XY: 5666 AN XY: 73846

African (AFR) AF: 0.168 AC: 6949 AN: 41292

American (AMR) AF: 0.0965 AC: 1469 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3470

East Asian (EAS) AF: 0.215 AC: 1110 AN: 5154

South Asian (SAS) AF: 0.0866 AC: 415 AN: 4792

European-Finnish (FIN) AF: 0.0184 AC: 187 AN: 10164

Middle Eastern (MID) AF: 0.0483 AC: 14 AN: 290

European-Non Finnish (NFE) AF: 0.0137 AC: 931 AN: 67894

Other (OTH) AF: 0.0846 AC: 178 AN: 2104

Alfa AF: 0.0371 Hom.: 1290

Bravo AF: 0.0866

Asia WGS AF: 0.165 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.44
PhyloP100		-0.73
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: rs10493423; hg19: chr1-67837158;