chr1-67307966-T-C

Position:

• chr1-67307966-T-C

Variant summary

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

The NM_001374259.2(IL12RB2):​c.-126T>C variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,776 control chromosomes in the GnomAD database, including 13,276 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (13271 hom., cov: 31)
  • Exomes 𝑓: 0.37 (5 hom.)
• Consequence: IL12RB2 NM_001374259.2 splice_region, 5_prime_UTR
• Scores: Splicing: ADA: 0.00008444
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12RB2	NM_001374259.2	c.-126T>C		splice_region_variant, 5_prime_UTR_variant	1/17	ENST00000674203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB2	ENST00000674203.2	c.-126T>C		splice_region_variant, 5_prime_UTR_variant	1/17		NM_001374259.2	P1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62000 AN: 151598 Hom.: 13253 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.368 AC: 25 AN: 68 Hom.: 5 Cov.: 0 AF XY: 0.354 AC XY: 17 AN XY: 48

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.409 AC: 62071 AN: 151708 Hom.: 13271 Cov.: 31 AF XY: 0.402 AC XY: 29773 AN XY: 74140

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.440

Alfa AF: 0.388 Hom.: 4458

Bravo AF: 0.426

Asia WGS AF: 0.354 AC: 1221 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.6
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000084
dbscSNV1_RF	Benign	0.044
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: rs11209046; hg19: chr1-67773649;