Genetic Variant NM_021643.4: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

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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