dbSNP rs199952311: TRIB1:p.Phe213Phe (chr8-125433595-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_025195.4(TRIB1):c.639C>T(p.Phe213Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,608,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TRIB1
NM_025195.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.23

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 8-125433595-C-T is Benign according to our data. Variant chr8-125433595-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 732886.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.23 with no splicing effect.

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.639C>T	p.Phe213Phe	synonymous	Exon 2 of 3	NP_079471.1	Q96RU8-1
	TRIB1	NM_001282985.2		c.141C>T	p.Phe47Phe	synonymous	Exon 2 of 3	NP_001269914.1	Q96RU8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIB1	ENST00000311922.4	TSL:1 MANE Select	c.639C>T	p.Phe213Phe	synonymous	Exon 2 of 3	ENSP00000312150.3	Q96RU8-1
TRIB1	ENST00000519576.1	TSL:1	c.-214C>T		5_prime_UTR	Exon 1 of 2	ENSP00000428879.1	E5RFH4
TRIB1	ENST00000520847.1	TSL:2	c.141C>T	p.Phe47Phe	synonymous	Exon 2 of 3	ENSP00000429063.1	Q96RU8-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

245704

AF XY:

0.0000224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000274

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1456236

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

723260

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33398

American (AMR)

AF:

0.00

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39566

South Asian (SAS)

AF:

0.00

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52754

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5434

European-Non Finnish (NFE)

AF:

0.0000208

AC:

AN:

1107952

Other (OTH)

AF:

0.00

AC:

AN:

60158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000394

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000329

Hom.:

Bravo

AF:

0.0000264

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

2.2

PromoterAI

-0.030

Neutral

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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