1-67307966-T-C

Variant names:

• chr1-67307966-T-C
• rs11209046
• NM_001374259.2:c.-126T>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.-126T>C variant causes a splice region 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
• Scores: Splicing: ADA: 0.00008444
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 9 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374259.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	NM_001374259.2	MANE Select	c.-126T>C		splice_region	Exon 1 of 17	NP_001361188.1
	IL12RB2	NM_001374259.2	MANE Select	c.-126T>C		5_prime_UTR	Exon 1 of 17	NP_001361188.1
	IL12RB2	NM_001559.3		c.-38T>C		splice_region	Exon 1 of 16	NP_001550.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	ENST00000674203.2	MANE Select	c.-126T>C		splice_region	Exon 1 of 17	ENSP00000501329.1
	IL12RB2	ENST00000262345.5	TSL:1	c.-38T>C		splice_region	Exon 1 of 16	ENSP00000262345.1
	IL12RB2	ENST00000544434.5	TSL:1	c.-38T>C		splice_region	Exon 1 of 14	ENSP00000442443.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 24 AN: 64

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.520 AC: 21534 AN: 41396

American (AMR) AF: 0.404 AC: 6161 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1586 AN: 3468

East Asian (EAS) AF: 0.235 AC: 1200 AN: 5108

South Asian (SAS) AF: 0.337 AC: 1620 AN: 4814

European-Finnish (FIN) AF: 0.263 AC: 2767 AN: 10508

Middle Eastern (MID) AF: 0.455 AC: 132 AN: 290

European-Non Finnish (NFE) AF: 0.381 AC: 25848 AN: 67866

Other (OTH) AF: 0.440 AC: 926 AN: 2106

Alfa AF: 0.388 Hom.: 7052

Bravo AF: 0.426

Asia WGS AF: 0.354 AC: 1221 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.6
DANN	Benign	0.68
PhyloP100		0.020
PromoterAI		0.15	Neutral
Mutation Taster		=290/10	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11209046; hg19: chr1-67773649;