Genetic Variant NM_025195.4:c.-419C>T (chr8-125430484-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025195.4(TRIB1):c.-419C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 163,086 control chromosomes in the GnomAD database, including 6,311 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 0.25 ( 5790 hom., cov: 33)

Exomes 𝑓: 0.28 ( 521 hom. )

Consequence

TRIB1
NM_025195.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

Publications

8 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.356 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIB1	NM_025195.4	MANE Select	c.-419C>T		5_prime_UTR	Exon 1 of 3	NP_079471.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIB1	ENST00000311922.4	TSL:1 MANE Select	c.-419C>T		5_prime_UTR	Exon 1 of 3	ENSP00000312150.3

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37777

AN:

152050

Hom.:

5789

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0665

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.275

GnomAD4 exome

AF:

0.280

AC:

3057

AN:

10918

Hom.:

521

Cov.:

AF XY:

0.290

AC XY:

1681

AN XY:

5788

show subpopulations

African (AFR)

AF:

0.0605

AC:

AN:

380

American (AMR)

AF:

0.211

AC:

AN:

204

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

107

AN:

428

East Asian (EAS)

AF:

0.154

AC:

AN:

570

South Asian (SAS)

AF:

0.362

AC:

461

AN:

1274

European-Finnish (FIN)

AF:

0.305

AC:

158

AN:

518

Middle Eastern (MID)

AF:

0.375

AC:

AN:

European-Non Finnish (NFE)

AF:

0.289

AC:

1979

AN:

6852

Other (OTH)

AF:

0.281

AC:

183

AN:

652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

111

222

333

444

555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.248

AC:

37771

AN:

152168

Hom.:

5790

Cov.:

AF XY:

0.252

AC XY:

18756

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0664

AC:

2759

AN:

41568

American (AMR)

AF:

0.265

AC:

4055

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1205

AN:

3470

East Asian (EAS)

AF:

0.174

AC:

898

AN:

5160

South Asian (SAS)

AF:

0.371

AC:

1789

AN:

4826

European-Finnish (FIN)

AF:

0.348

AC:

3686

AN:

10588

Middle Eastern (MID)

AF:

0.305

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.331

AC:

22478

AN:

67960

Other (OTH)

AF:

0.270

AC:

570

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1378

2757

4135

5514

6892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.299

Hom.:

2777

Bravo

AF:

0.229

Asia WGS

AF:

0.249

AC:

863

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

1.3

PromoterAI

0.029

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over