8-125435066-C-T

Variant names:

• chr8-125435066-C-T
• rs2385114
• NM_025195.4:c.654-940C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025195.4. 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
	TRIB1	NM_025195.4	MANE Select	c.654-940C>T		intron	N/A	NP_079471.1	Q96RU8-1
	TRIB1	NM_001282985.2		c.156-940C>T		intron	N/A	NP_001269914.1	Q96RU8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIB1	ENST00000311922.4	TSL:1 MANE Select	c.654-940C>T		intron	N/A	ENSP00000312150.3	Q96RU8-1
	TRIB1	ENST00000519576.1	TSL:1	c.-40-940C>T		intron	N/A	ENSP00000428879.1	E5RFH4
	TRIB1	ENST00000520847.1	TSL:2	c.156-940C>T		intron	N/A	ENSP00000429063.1	Q96RU8-2

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

African (AFR) AF: 0.726 AC: 30063 AN: 41436

American (AMR) AF: 0.650 AC: 9934 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2034 AN: 3468

East Asian (EAS) AF: 0.683 AC: 3521 AN: 5158

South Asian (SAS) AF: 0.738 AC: 3561 AN: 4822

European-Finnish (FIN) AF: 0.517 AC: 5448 AN: 10542

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33159 AN: 67934

Other (OTH) AF: 0.598 AC: 1262 AN: 2110

Alfa AF: 0.524 Hom.: 35519

Bravo AF: 0.601

Asia WGS AF: 0.688 AC: 2390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.32
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2385114; hg19: chr8-126447308;