rs742605

Variant names:

• chr20-372441-A-G
• rs742605
• ENST00000615226.5:c.-407-3004A>G

Variant summary

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

The ENST00000615226.5(TRIB3):​c.-407-3004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,100 control chromosomes in the GnomAD database, including 9,560 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 (9560 hom., cov: 33)
• Consequence: TRIB3 ENST00000615226.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 11 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIB3	ENST00000615226.5	TSL:3	c.-407-3004A>G		intron	N/A	ENSP00000478194.2	A0A087WTX3

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50006 AN: 151982 Hom.: 9551 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.329 AC: 50026 AN: 152100 Hom.: 9560 Cov.: 33 AF XY: 0.329 AC XY: 24480 AN XY: 74364

African (AFR) AF: 0.136 AC: 5650 AN: 41552

American (AMR) AF: 0.277 AC: 4233 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3468

East Asian (EAS) AF: 0.329 AC: 1697 AN: 5162

South Asian (SAS) AF: 0.347 AC: 1673 AN: 4816

European-Finnish (FIN) AF: 0.452 AC: 4780 AN: 10566

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29543 AN: 67952

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.396 Hom.: 21001

Bravo AF: 0.308

Asia WGS AF: 0.266 AC: 924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.60
PhyloP100		0.28

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs742605;

hg19: chr20-353085;