rs143743442

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_013254.4(TBK1):c.87+49G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000872 in 1,319,202 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 2 hom. )

Consequence

TBK1
NM_013254.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.07

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

frontotemporal dementia and/or amyotrophic lateral sclerosis 4
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
frontotemporal dementia with motor neuron disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
autoinflammation with arthritis and vasculitis
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

TBK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 12-64456006-G-C is Benign according to our data. Variant chr12-64456006-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1217885.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00449 (683/152248) while in subpopulation AFR AF = 0.0155 (644/41546). AF 95% confidence interval is 0.0145. There are 4 homozygotes in GnomAd4. There are 323 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013254.4. 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
	TBK1	NM_013254.4	MANE Select	c.87+49G>C		intron	N/A	NP_037386.1	Q9UHD2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBK1	ENST00000331710.10	TSL:1 MANE Select	c.87+49G>C	intron	N/A	ENSP00000329967.5	Q9UHD2
TBK1	ENST00000650790.1		c.87+49G>C	intron	N/A	ENSP00000498995.1	Q9UHD2
TBK1	ENST00000911930.1		c.87+49G>C	intron	N/A	ENSP00000581989.1

Frequencies

GnomAD3 genomes

AF:

0.00449

AC:

683

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

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:

0.0000735

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00132

AC:

244

AN:

185236

AF XY:

0.000821

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.000983

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000829

Gnomad OTH exome

AF:

0.000649

GnomAD4 exome

AF:

0.000401

AC:

468

AN:

1166954

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

192

AN XY:

589174

show subpopulations

African (AFR)

AF:

0.0139

AC:

367

AN:

26376

American (AMR)

AF:

0.00103

AC:

AN:

30986

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21802

East Asian (EAS)

AF:

0.00

AC:

AN:

37788

South Asian (SAS)

AF:

0.00

AC:

AN:

72440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4782

European-Non Finnish (NFE)

AF:

0.0000241

AC:

AN:

871006

Other (OTH)

AF:

0.000956

AC:

AN:

50234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

115

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:

0.00449

AC:

683

AN:

152248

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

323

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0155

AC:

644

AN:

41546

American (AMR)

AF:

0.00183

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67990

Other (OTH)

AF:

0.00284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

107

143

179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00214

Hom.:

Bravo

AF:

0.00491

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

-0.98

CADD

Benign

0.16

(source)

DANN

Benign

0.39

PhyloP100

-2.1

PromoterAI

-0.0070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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