NM_001374259.2:c.807+38A>T

Variant names:

• chr1-67329767-A-T
• rs2307149
• NM_001374259.2:c.807+38A>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.807+38A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00472 in 1,390,442 control chromosomes in the GnomAD database, including 198 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 0.022 (96 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (102 hom.)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0738 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.807+38A>T		intron	N/A	NP_001361188.1	Q99665-1
	IL12RB2	NM_001559.3		c.807+38A>T		intron	N/A	NP_001550.1	Q99665-1
	IL12RB2	NM_001258215.1		c.807+38A>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.807+38A>T		intron	N/A	ENSP00000501329.1	Q99665-1
	IL12RB2	ENST00000262345.5	TSL:1	c.807+38A>T		intron	N/A	ENSP00000262345.1	Q99665-1
	IL12RB2	ENST00000544434.5	TSL:1	c.807+38A>T		intron	N/A	ENSP00000442443.1	Q99665-3

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3328 AN: 152214 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00745

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00612 AC: 1536 AN: 250842 AF XY: 0.00459

Gnomad AFR exome AF: 0.0785

Gnomad AMR exome AF: 0.00521

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000565

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00260 AC: 3221 AN: 1238110 Hom.: 102 Cov.: 18 AF XY: 0.00229 AC XY: 1434 AN XY: 627372

African (AFR) AF: 0.0779 AC: 2275 AN: 29198

American (AMR) AF: 0.00560 AC: 249 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.000768 AC: 19 AN: 24728

East Asian (EAS) AF: 0.00 AC: 0 AN: 38690

South Asian (SAS) AF: 0.000110 AC: 9 AN: 81718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00577 AC: 28 AN: 4852

European-Non Finnish (NFE) AF: 0.000383 AC: 348 AN: 908222

Other (OTH) AF: 0.00554 AC: 293 AN: 52920

GnomAD4 genome AF: 0.0219 AC: 3336 AN: 152332 Hom.: 96 Cov.: 32 AF XY: 0.0214 AC XY: 1592 AN XY: 74502

African (AFR) AF: 0.0760 AC: 3157 AN: 41558

American (AMR) AF: 0.00738 AC: 113 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68028

Other (OTH) AF: 0.0128 AC: 27 AN: 2110

Alfa AF: 0.0109 Hom.: 8

Bravo AF: 0.0248

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.62
DANN	Benign	0.63
PhyloP100		-0.15
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: rs2307149; hg19: chr1-67795450;