NM_021643.4:c.*606T>G

Variant names:

• chr2-12741400-T-G
• rs1176
• NM_021643.4:c.*606T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ENSG00000225649 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021643.4. 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
	TRIB2	NM_021643.4	MANE Select	c.*606T>G		3_prime_UTR	Exon 3 of 3	NP_067675.1
	TRIB2	NR_027303.2		n.1443T>G		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIB2	ENST00000155926.9	TSL:1 MANE Select	c.*606T>G		3_prime_UTR	Exon 3 of 3	ENSP00000155926.4
	TRIB2	ENST00000381465.2	TSL:2	c.*606T>G		3_prime_UTR	Exon 3 of 3	ENSP00000370874.2
	ENSG00000225649	ENST00000848764.1		n.325-3878A>C		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.100 AC: 3 AN: 30

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.143 AC: 2 AN: 14

European-Finnish (FIN) AF: 0.110 AC: 43 AN: 390

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.134 AC: 37 AN: 276

Other (OTH) AF: 0.00 AC: 0 AN: 12

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

African (AFR) AF: 0.0270 AC: 1121 AN: 41570

American (AMR) AF: 0.0929 AC: 1421 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3470

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5188

South Asian (SAS) AF: 0.0493 AC: 238 AN: 4828

European-Finnish (FIN) AF: 0.101 AC: 1069 AN: 10608

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10435 AN: 68020

Other (OTH) AF: 0.101 AC: 213 AN: 2110

Alfa AF: 0.136 Hom.: 2191

Bravo AF: 0.0948

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1176; hg19: chr2-12881526;