20-371300-T-G

Variant names:

• chr20-371300-T-G
• rs6051520
• ENST00000615226.5:c.-407-4145T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000615226.5(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 ENST00000615226.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• Publications: 15 publications found

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]

TRIB3 Gene-Disease associations (from GenCC):

• cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000615226.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIB3	ENST00000615226.5	TSL:3	c.-407-4145T>G		intron	N/A	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

African (AFR) AF: 0.539 AC: 22357 AN: 41488

American (AMR) AF: 0.254 AC: 3876 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1165 AN: 3468

East Asian (EAS) AF: 0.356 AC: 1841 AN: 5172

South Asian (SAS) AF: 0.435 AC: 2098 AN: 4828

European-Finnish (FIN) AF: 0.201 AC: 2130 AN: 10600

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15801 AN: 67974

Other (OTH) AF: 0.337 AC: 712 AN: 2114

Alfa AF: 0.265 Hom.: 27179

Bravo AF: 0.340

Asia WGS AF: 0.399 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.7
DANN	Benign	0.87
PhyloP100		0.32

Splicing

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

Other links and lift over

dbSNP: rs6051520; hg19: chr20-351944;