1-67321603-T-C

Variant names:

• chr1-67321603-T-C
• rs2307147
• NM_001374259.2:c.78T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001374259.2(IL12RB2):​c.78T>C​(p.Asp26Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,589,766 control chromosomes in the GnomAD database, including 1,638 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (845 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (793 hom.)
• Consequence: IL12RB2 NM_001374259.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001872
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.01
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 1-67321603-T-C is Benign according to our data. Variant chr1-67321603-T-C is described in ClinVar as Benign. ClinVar VariationId is 1169445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 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.78T>C	p.Asp26Asp	splice_region synonymous	Exon 4 of 17	NP_001361188.1
	IL12RB2	NM_001559.3		c.78T>C	p.Asp26Asp	splice_region synonymous	Exon 3 of 16	NP_001550.1
	IL12RB2	NM_001258215.1		c.78T>C	p.Asp26Asp	splice_region synonymous	Exon 3 of 14	NP_001245144.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	ENST00000674203.2	MANE Select	c.78T>C	p.Asp26Asp	splice_region synonymous	Exon 4 of 17	ENSP00000501329.1
	IL12RB2	ENST00000262345.5	TSL:1	c.78T>C	p.Asp26Asp	splice_region synonymous	Exon 3 of 16	ENSP00000262345.1
	IL12RB2	ENST00000544434.5	TSL:1	c.78T>C	p.Asp26Asp	splice_region synonymous	Exon 3 of 14	ENSP00000442443.1

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8650 AN: 152134 Hom.: 844 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0406

GnomAD2 exomes AF: 0.0157 AC: 3934 AN: 251054 AF XY: 0.0110

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.00954

Gnomad ASJ exome AF: 0.00347

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000502

Gnomad OTH exome AF: 0.00522

GnomAD4 exome AF: 0.00601 AC: 8642 AN: 1437514 Hom.: 793 Cov.: 27 AF XY: 0.00518 AC XY: 3716 AN XY: 716826

African (AFR) AF: 0.211 AC: 6895 AN: 32702

American (AMR) AF: 0.0102 AC: 458 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 90 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.000420 AC: 36 AN: 85742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53250

Middle Eastern (MID) AF: 0.00875 AC: 50 AN: 5716

European-Non Finnish (NFE) AF: 0.000292 AC: 318 AN: 1090330

Other (OTH) AF: 0.0134 AC: 795 AN: 59500

GnomAD4 genome AF: 0.0570 AC: 8672 AN: 152252 Hom.: 845 Cov.: 32 AF XY: 0.0545 AC XY: 4054 AN XY: 74442

African (AFR) AF: 0.200 AC: 8310 AN: 41500

American (AMR) AF: 0.0154 AC: 235 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68030

Other (OTH) AF: 0.0402 AC: 85 AN: 2114

Alfa AF: 0.0220 Hom.: 931

Bravo AF: 0.0650

Asia WGS AF: 0.0140 AC: 49 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IL12RB2-related disorder Benign:1

May 02, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	2.5
DANN	Benign	0.50
PhyloP100		-1.0
Mutation Taster		=79/21	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.0060
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: rs2307147; hg19: chr1-67787286;