rs6037439

Variant names:

• chr20-367544-T-A
• rs6037439
• ENST00000615226.5:c.-408+4631T>A

Your query was ambiguous. Multiple possible variants found:

• chr20-367544-T-A
• chr20-367544-T-G

Variant summary

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

The ENST00000615226.5(TRIB3):​c.-408+4631T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,006 control chromosomes in the GnomAD database, including 4,251 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 0.23 (4251 hom., cov: 32)
• Consequence: TRIB3 ENST00000615226.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 1 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIB3	ENST00000615226.5	c.-408+4631T>A		intron_variant	Intron 1 of 5	3		ENSP00000478194.2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34399 AN: 151888 Hom.: 4246 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.227 AC: 34430 AN: 152006 Hom.: 4251 Cov.: 32 AF XY: 0.229 AC XY: 17032 AN XY: 74302

African (AFR) AF: 0.138 AC: 5701 AN: 41392

American (AMR) AF: 0.327 AC: 5003 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 574 AN: 3468

East Asian (EAS) AF: 0.168 AC: 866 AN: 5168

South Asian (SAS) AF: 0.273 AC: 1314 AN: 4818

European-Finnish (FIN) AF: 0.271 AC: 2870 AN: 10584

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17442 AN: 67974

Other (OTH) AF: 0.198 AC: 418 AN: 2110

Alfa AF: 0.232 Hom.: 563

Bravo AF: 0.225

Asia WGS AF: 0.189 AC: 656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.78
PhyloP100		-0.29

Splicing

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

Other links and lift over

dbSNP: rs6037439; hg19: chr20-348188;