NM_013254.4:c.229-4dupT

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_013254.4(TBK1):c.229-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,208,146 control chromosomes in the GnomAD database, including 369,857 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60292 hom., cov: 0)

Exomes 𝑓: 0.79 ( 309565 hom. )

Consequence

TBK1
NM_013254.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.04

Variant links:

Genes affected

TBK1 (HGNC:11584): (TANK binding kinase 1) The NF-kappa-B (NFKB) complex of proteins is inhibited by I-kappa-B (IKB) proteins, which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the IKB proteins by IKB kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation and nuclear translocation of the NFKB complex. The protein encoded by this gene is similar to IKB kinases and can mediate NFKB activation in response to certain growth factors. The protein is also an important kinase for antiviral innate immunity response. [provided by RefSeq, Sep 2021]

TBK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-64464320-A-AT is Benign according to our data. Variant chr12-64464320-A-AT is described in ClinVar as [Benign]. Clinvar id is 403521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TBK1	NM_013254.4 link	c.229-4dupT	splice_region_variant, intron_variant	Intron 3 of 20	ENST00000331710.10	NP_037386.1	Q9UHD2
TBK1	XM_005268809.2 link	c.229-4dupT	splice_region_variant, intron_variant	Intron 3 of 20		XP_005268866.1	Q9UHD2
TBK1	XM_005268810.2 link	c.229-4dupT	splice_region_variant, intron_variant	Intron 3 of 20		XP_005268867.1	Q9UHD2
TBK1	XR_007063071.1 link	n.328-4dupT	splice_region_variant, intron_variant	Intron 3 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBK1	ENST00000331710.10 link	c.229-14_229-13insT		intron_variant	Intron 3 of 20	1	NM_013254.4	ENSP00000329967.5		Q9UHD2

Frequencies

GnomAD3 genomes

AF:

0.893

AC:

134384

AN:

150500

Hom.:

60254

Cov.:

show subpopulations

Gnomad AFR

AF:

0.806

Gnomad AMI

AF:

0.851

Gnomad AMR

AF:

0.936

Gnomad ASJ

AF:

0.955

Gnomad EAS

AF:

0.919

Gnomad SAS

AF:

0.844

Gnomad FIN

AF:

0.960

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.925

Gnomad OTH

AF:

0.907

GnomAD3 exomes

AF:

0.797

AC:

122184

AN:

153360

Hom.:

46208

AF XY:

0.793

AC XY:

66132

AN XY:

83392

show subpopulations

Gnomad AFR exome

AF:

0.718

Gnomad AMR exome

AF:

0.828

Gnomad ASJ exome

AF:

0.810

Gnomad EAS exome

AF:

0.790

Gnomad SAS exome

AF:

0.720

Gnomad FIN exome

AF:

0.853

Gnomad NFE exome

AF:

0.811

Gnomad OTH exome

AF:

0.792

GnomAD4 exome

AF:

0.787

AC:

832703

AN:

1057534

Hom.:

309565

Cov.:

AF XY:

0.785

AC XY:

414192

AN XY:

527788

show subpopulations

Gnomad4 AFR exome

AF:

0.686

Gnomad4 AMR exome

AF:

0.817

Gnomad4 ASJ exome

AF:

0.795

Gnomad4 EAS exome

AF:

0.766

Gnomad4 SAS exome

AF:

0.710

Gnomad4 FIN exome

AF:

0.821

Gnomad4 NFE exome

AF:

0.795

Gnomad4 OTH exome

AF:

0.779

GnomAD4 genome

AF:

0.893

AC:

134477

AN:

150612

Hom.:

60292

Cov.:

AF XY:

0.894

AC XY:

65721

AN XY:

73536

show subpopulations

Gnomad4 AFR

AF:

0.806

Gnomad4 AMR

AF:

0.936

Gnomad4 ASJ

AF:

0.955

Gnomad4 EAS

AF:

0.919

Gnomad4 SAS

AF:

0.844

Gnomad4 FIN

AF:

0.960

Gnomad4 NFE

AF:

0.925

Gnomad4 OTH

AF:

0.907

Alfa

AF:

0.816

Hom.:

5204

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Glaucoma 1, open angle, P

Benign:2

Apr 22, 2016

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 30, 2015

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Frontotemporal dementia and/or amyotrophic lateral sclerosis 4

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Oct 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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