dbSNP rs1057001: TRIB2: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:

Genome browser will be placed here

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over