Variant 8-125436255-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_025195.4(TRIB1):c.903C>T(p.Phe301=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,614,110 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 62 hom. )

Consequence

TRIB1
NM_025195.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.28

Variant links:

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]

TRIB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 8-125436255-C-T is Benign according to our data. Variant chr8-125436255-C-T is described in ClinVar as [Benign]. Clinvar id is 770196.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00293 (446/152222) while in subpopulation EAS AF= 0.0195 (101/5172). AF 95% confidence interval is 0.0164. There are 6 homozygotes in gnomad4. There are 223 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIB1	NM_025195.4 linkuse as main transcript	c.903C>T	p.Phe301=	synonymous_variant	3/3	ENST00000311922.4
TRIB1	NM_001282985.2 linkuse as main transcript	c.405C>T	p.Phe135=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIB1	ENST00000311922.4 linkuse as main transcript	c.903C>T	p.Phe301=	synonymous_variant	3/3	1	NM_025195.4	P1	Q96RU8-1
TRIB1	ENST00000519576.1 linkuse as main transcript	c.210C>T	p.Phe70=	synonymous_variant	2/2	1
TRIB1	ENST00000520847.1 linkuse as main transcript	c.405C>T	p.Phe135=	synonymous_variant	3/3	2			Q96RU8-2

Frequencies

GnomAD3 genomes

AF:

0.00291

AC:

443

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0179

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0193

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00756

AC:

1900

AN:

251488

Hom.:

AF XY:

0.00594

AC XY:

808

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.0408

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.0198

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00537

GnomAD4 exome

AF:

0.00191

AC:

2795

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

1230

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.0392

Gnomad4 ASJ exome

AF:

0.00256

Gnomad4 EAS exome

AF:

0.0146

Gnomad4 SAS exome

AF:

0.000823

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000124

Gnomad4 OTH exome

AF:

0.00263

GnomAD4 genome

AF:

0.00293

AC:

446

AN:

152222

Hom.:

Cov.:

AF XY:

0.00300

AC XY:

223

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.0180

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.0195

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.00530

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over