20-371300-T-G

Position:

• chr20-371300-T-G

Variant summary

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

The ENST00000615226.4(TRIB3):​c.-407-4145T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,130 control chromosomes in the GnomAD database, including 9,848 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 0.33 (9848 hom., cov: 33)
• Consequence: TRIB3 ENST00000615226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319

Genes affected

TRIB3 (HGNC:16228): (tribbles pseudokinase 3) The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. The encoded protein is a negative regulator of NF-kappaB and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein can negatively regulate the cell survival serine-threonine kinase AKT1. Differential promoter usage and alternate splicing result in multiple transcript variants. [provided by RefSeq, Jul 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.371300T>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIB3	ENST00000615226.4	c.-407-4145T>G		intron_variant		3		ENSP00000478194.2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50257 AN: 152012 Hom.: 9824 Cov.: 33

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.341

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50301 AN: 152130 Hom.: 9848 Cov.: 33 AF XY: 0.329 AC XY: 24436 AN XY: 74386

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.337

Alfa AF: 0.254 Hom.: 11953

Bravo AF: 0.340

Asia WGS AF: 0.399 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.7
DANN	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6051520; hg19: chr20-351944;