rs1176

chr2-12741400-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021643.4(TRIB2):c.*606T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 153,030 control chromosomes in the GnomAD database, including 1,040 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 0.099 (1034 hom., cov: 32)
  • Exomes 𝑓: 0.12 (6 hom.)
• Consequence: TRIB2 NM_021643.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19

Genes affected

TRIB2 (HGNC:30809): (tribbles pseudokinase 2) This gene encodes one of three members of the Tribbles family. The Tribbles members share a Trb domain, which is homologous to protein serine-threonine kinases, but lacks the active site lysine and probably lacks a catalytic function. The Tribbles proteins interact and modulate the activity of signal transduction pathways in a number of physiological and pathological processes. This Tribbles member induces apoptosis of cells mainly of the hematopoietic origin. It has been identified as a protein up-regulated by inflammatory stimuli in myeloid (THP-1) cells, and also as an oncogene that inactivates the transcription factor C/EBPalpha (CCAAT/enhancer-binding protein alpha) and causes acute myelogenous leukemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIB2	NM_021643.4	c.*606T>G		3_prime_UTR_variant	3/3	ENST00000155926.9
TRIB2	NR_027303.2	n.1443T>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIB2	ENST00000155926.9	c.*606T>G		3_prime_UTR_variant	3/3	1	NM_021643.4	P1
TRIB2	ENST00000381465.2	c.*606T>G		3_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15019 AN: 152182 Hom.: 1033 Cov.: 32

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.0931

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0486

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.116 AC: 85 AN: 730 Hom.: 6 Cov.: 0 AF XY: 0.119 AC XY: 49 AN XY: 412

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0986 AC: 15017 AN: 152300 Hom.: 1034 Cov.: 32 AF XY: 0.0962 AC XY: 7160 AN XY: 74466

Gnomad4 AFR AF: 0.0270

Gnomad4 AMR AF: 0.0929

Gnomad4 ASJ AF: 0.0839

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0493

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.101

Alfa AF: 0.141 Hom.: 1608

Bravo AF: 0.0948

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	13
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1176; hg19: chr2-12881526;