Genetic Variant TRIB2:c.*606T>G (chr2-12741400-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.19

Publications

8 publications found

Variant links:

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]

TRIB2 links:

ENSG00000225649 (HGNC:):

ENSG00000225649 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIB2	NM_021643.4 link	c.*606T>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000155926.9	NP_067675.1	Q92519
TRIB2	NR_027303.2 link	n.1443T>G		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIB2	ENST00000155926.9 link	c.*606T>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_021643.4	ENSP00000155926.4		Q92519

Frequencies

GnomAD3 genomes

AF:

0.0987

AC:

15019

AN:

152182

Hom.:

1033

Cov.:

show subpopulations

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:

AN:

730

Hom.:

Cov.:

AF XY:

0.119

AC XY:

AN XY:

412

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.100

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.143

AC:

AN:

European-Finnish (FIN)

AF:

0.110

AC:

AN:

390

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.134

AC:

AN:

276

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0986

AC:

15017

AN:

152300

Hom.:

1034

Cov.:

AF XY:

0.0962

AC XY:

7160

AN XY:

74466

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.153

AC:

10435

AN:

68020

Other (OTH)

AF:

0.101

AC:

213

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

695

1390

2085

2780

3475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.136

Hom.:

2191

Bravo

AF:

0.0948

Asia WGS

AF:

0.0220

AC:

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

(source)

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)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over