8-125435066-C-T

Position:

• chr8-125435066-C-T

Variant summary

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

The NM_025195.4(TRIB1):​c.654-940C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,950 control chromosomes in the GnomAD database, including 27,278 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 0.59 (27278 hom., cov: 31)
• Consequence: TRIB1 NM_025195.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290

Genes affected

TRIB1 (HGNC:16891): (tribbles pseudokinase 1) Enables mitogen-activated protein kinase kinase binding activity and protein kinase inhibitor activity. Involved in several processes, including JNK cascade; negative regulation of lipopolysaccharide-mediated signaling pathway; and regulation of protein kinase activity. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIB1	NM_025195.4	c.654-940C>T		intron_variant		ENST00000311922.4
TRIB1	NM_001282985.2	c.156-940C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIB1	ENST00000311922.4	c.654-940C>T		intron_variant		1	NM_025195.4	P1
TRIB1	ENST00000519576.1	c.-40-940C>T		intron_variant		1
TRIB1	ENST00000520847.1	c.156-940C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89338 AN: 151832 Hom.: 27235 Cov.: 31

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.589 AC: 89442 AN: 151950 Hom.: 27278 Cov.: 31 AF XY: 0.599 AC XY: 44489 AN XY: 74264

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.598

Alfa AF: 0.514 Hom.: 26849

Bravo AF: 0.601

Asia WGS AF: 0.688 AC: 2390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.32

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: rs2385114; hg19: chr8-126447308;