17-47698708-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001394755.1(TBKBP1):​c.567C>T​(p.Pro189Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000791 in 1,607,584 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00058 ( 4 hom. )

Consequence

TBKBP1
NM_001394755.1 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.594
Variant links:
Genes affected
TBKBP1 (HGNC:30140): (TBK1 binding protein 1) TBKBP1 is an adaptor protein that binds to TBK1 (MIM 604834) and is part of the interaction network in the TNF (MIM 191160)/NFKB (see MIM 164011) pathway (Bouwmeester et al., 2004 [PubMed 14743216]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 17-47698708-C-T is Benign according to our data. Variant chr17-47698708-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647876.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.594 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBKBP1NM_001394755.1 linkc.567C>T p.Pro189Pro synonymous_variant Exon 5 of 10 ENST00000578982.6 NP_001381684.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBKBP1ENST00000578982.6 linkc.567C>T p.Pro189Pro synonymous_variant Exon 5 of 10 3 NM_001394755.1 ENSP00000462339.2 A7MCY6-1J3KS71
TBKBP1ENST00000361722.7 linkc.567C>T p.Pro189Pro synonymous_variant Exon 4 of 9 1 ENSP00000354777.3 A7MCY6-1
TBKBP1ENST00000537587.6 linkc.567C>T p.Pro189Pro synonymous_variant Exon 5 of 5 3 ENSP00000446365.2 F5H1U4

Frequencies

GnomAD3 genomes
AF:
0.00285
AC:
433
AN:
152142
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00881
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00203
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000382
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.000972
AC:
231
AN:
237570
Hom.:
1
AF XY:
0.000784
AC XY:
101
AN XY:
128764
show subpopulations
Gnomad AFR exome
AF:
0.00884
Gnomad AMR exome
AF:
0.00179
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000347
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000363
Gnomad OTH exome
AF:
0.000864
GnomAD4 exome
AF:
0.000575
AC:
837
AN:
1455324
Hom.:
4
Cov.:
32
AF XY:
0.000535
AC XY:
387
AN XY:
723348
show subpopulations
Gnomad4 AFR exome
AF:
0.00996
Gnomad4 AMR exome
AF:
0.00175
Gnomad4 ASJ exome
AF:
0.0000387
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.0000472
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000326
Gnomad4 OTH exome
AF:
0.000848
GnomAD4 genome
AF:
0.00286
AC:
435
AN:
152260
Hom.:
0
Cov.:
31
AF XY:
0.00282
AC XY:
210
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00883
Gnomad4 AMR
AF:
0.00203
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000382
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00141
Hom.:
0
Bravo
AF:
0.00315
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

TBKBP1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.36
DANN
Benign
0.44

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.

Other links and lift over

dbSNP: rs141010554; hg19: chr17-45776074; API