Genetic Variant NM_021643.4:c.*858T>A (chr2-12741652-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021643.4(TRIB2):c.*858T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,286 control chromosomes in the GnomAD database, including 16,191 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 0.45 ( 16167 hom., cov: 33)

Exomes 𝑓: 0.57 ( 24 hom. )

Consequence

TRIB2
NM_021643.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.406

Publications

15 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIB2	NM_021643.4 link	c.*858T>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000155926.9	NP_067675.1	Q92519
TRIB2	NR_027303.2 link	n.1695T>A		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.*858T>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_021643.4	ENSP00000155926.4		Q92519

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67864

AN:

152036

Hom.:

16152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.476

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.832

Gnomad SAS

AF:

0.584

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.472

Gnomad OTH

AF:

0.442

GnomAD4 exome

AF:

0.568

AC:

AN:

132

Hom.:

Cov.:

AF XY:

0.565

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.587

AC:

AN:

126

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.569

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.446

AC:

67909

AN:

152154

Hom.:

16167

Cov.:

AF XY:

0.452

AC XY:

33598

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.308

AC:

12781

AN:

41502

American (AMR)

AF:

0.446

AC:

6814

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

1739

AN:

3472

East Asian (EAS)

AF:

0.832

AC:

4303

AN:

5174

South Asian (SAS)

AF:

0.584

AC:

2818

AN:

4824

European-Finnish (FIN)

AF:

0.556

AC:

5879

AN:

10574

Middle Eastern (MID)

AF:

0.370

AC:

108

AN:

292

European-Non Finnish (NFE)

AF:

0.472

AC:

32086

AN:

67998

Other (OTH)

AF:

0.448

AC:

947

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1908

3816

5724

7632

9540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.452

Hom.:

2138

Bravo

AF:

0.432

Asia WGS

AF:

0.637

AC:

2214

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.091

(source)

DANN

Benign

0.74

PhyloP100

-0.41

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over