rs1057001

Positions:

• chr2-12741652-T-A
• chr2-12741652-T-C
• chr2-12741652-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TRIB2	NM_021643.4	c.*858T>A		3_prime_UTR_variant	3/3	ENST00000155926.9
TRIB2	NR_027303.2	n.1695T>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIB2	ENST00000155926.9	c.*858T>A		3_prime_UTR_variant	3/3	1	NM_021643.4	P1
TRIB2	ENST00000381465.2	c.*858T>A		3_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67864 AN: 152036 Hom.: 16152 Cov.: 33

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: 75 AN: 132 Hom.: 24 Cov.: 0 AF XY: 0.565 AC XY: 52 AN XY: 92

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.446 AC: 67909 AN: 152154 Hom.: 16167 Cov.: 33 AF XY: 0.452 AC XY: 33598 AN XY: 74386

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.448

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
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs1057001; hg19: chr2-12881778;