1-67322008-A-T

Variant names:

• chr1-67322008-A-T
• rs17129778
• NM_001374259.2:c.364+119A>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.364+119A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 880,290 control chromosomes in the GnomAD database, including 11,931 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 0.16 (2073 hom., cov: 31)
  • Exomes 𝑓: 0.16 (9858 hom.)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	NM_001374259.2	MANE Select	c.364+119A>T		intron	N/A	NP_001361188.1	Q99665-1
	IL12RB2	NM_001559.3		c.364+119A>T		intron	N/A	NP_001550.1	Q99665-1
	IL12RB2	NM_001258215.1		c.364+119A>T		intron	N/A	NP_001245144.1	Q99665-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	ENST00000674203.2	MANE Select	c.364+119A>T		intron	N/A	ENSP00000501329.1	Q99665-1
	IL12RB2	ENST00000262345.5	TSL:1	c.364+119A>T		intron	N/A	ENSP00000262345.1	Q99665-1
	IL12RB2	ENST00000544434.5	TSL:1	c.364+119A>T		intron	N/A	ENSP00000442443.1	Q99665-3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24659 AN: 151914 Hom.: 2067 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0579

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.155 AC: 113013 AN: 728258 Hom.: 9858 AF XY: 0.155 AC XY: 60422 AN XY: 389720

African (AFR) AF: 0.170 AC: 3304 AN: 19436

American (AMR) AF: 0.120 AC: 5043 AN: 42138

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 6509 AN: 21382

East Asian (EAS) AF: 0.0377 AC: 1365 AN: 36186

South Asian (SAS) AF: 0.117 AC: 8160 AN: 69918

European-Finnish (FIN) AF: 0.0855 AC: 3657 AN: 42794

Middle Eastern (MID) AF: 0.242 AC: 692 AN: 2858

European-Non Finnish (NFE) AF: 0.171 AC: 78104 AN: 457242

Other (OTH) AF: 0.170 AC: 6179 AN: 36304

GnomAD4 genome AF: 0.162 AC: 24694 AN: 152032 Hom.: 2073 Cov.: 31 AF XY: 0.158 AC XY: 11707 AN XY: 74316

African (AFR) AF: 0.170 AC: 7029 AN: 41438

American (AMR) AF: 0.162 AC: 2480 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3470

East Asian (EAS) AF: 0.0577 AC: 299 AN: 5184

South Asian (SAS) AF: 0.113 AC: 545 AN: 4818

European-Finnish (FIN) AF: 0.0802 AC: 848 AN: 10580

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11888 AN: 67960

Other (OTH) AF: 0.181 AC: 382 AN: 2106

Alfa AF: 0.0718 Hom.: 110

Bravo AF: 0.171

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.79
PhyloP100		0.040
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: rs17129778; hg19: chr1-67787691;