Variant rs201728462 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_013254.4(TBK1):c.1341-3del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00773 in 1,507,074 control chromosomes in the GnomAD database, including 48 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 46 hom. )

Consequence

TBK1
NM_013254.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.179

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-64488477-CT-C is Benign according to our data. Variant chr12-64488477-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 475934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-64488477-CT-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00602 (916/152120) while in subpopulation NFE AF= 0.00905 (615/67982). AF 95% confidence interval is 0.00845. There are 2 homozygotes in gnomad4. There are 452 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 916 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TBK1	NM_013254.4 linkuse as main transcript	c.1341-3del	splice_polypyrimidine_tract_variant, intron_variant	ENST00000331710.10
TBK1	XM_005268809.2 linkuse as main transcript	c.1341-3del	splice_polypyrimidine_tract_variant, intron_variant
TBK1	XM_005268810.2 linkuse as main transcript	c.1341-3del	splice_polypyrimidine_tract_variant, intron_variant
TBK1	XR_007063071.1 linkuse as main transcript	n.1440-3del	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBK1	ENST00000331710.10 linkuse as main transcript	c.1341-3del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_013254.4	P4

Frequencies

GnomAD3 genomes

AF:

0.00603

AC:

917

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00905

Gnomad OTH

AF:

0.00576

GnomAD3 exomes

AF:

0.00697

AC:

1245

AN:

178590

Hom.:

AF XY:

0.00713

AC XY:

696

AN XY:

97548

show subpopulations

Gnomad AFR exome

AF:

0.000928

Gnomad AMR exome

AF:

0.00290

Gnomad ASJ exome

AF:

0.00569

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00562

Gnomad FIN exome

AF:

0.0136

Gnomad NFE exome

AF:

0.00906

Gnomad OTH exome

AF:

0.00500

GnomAD4 exome

AF:

0.00792

AC:

10730

AN:

1354954

Hom.:

Cov.:

AF XY:

0.00803

AC XY:

5408

AN XY:

673192

show subpopulations

Gnomad4 AFR exome

AF:

0.000970

Gnomad4 AMR exome

AF:

0.00367

Gnomad4 ASJ exome

AF:

0.00591

Gnomad4 EAS exome

AF:

0.0000554

Gnomad4 SAS exome

AF:

0.00599

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.00858

Gnomad4 OTH exome

AF:

0.00690

GnomAD4 genome

AF:

0.00602

AC:

916

AN:

152120

Hom.:

Cov.:

AF XY:

0.00608

AC XY:

452

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00157

Gnomad4 AMR

AF:

0.00406

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00478

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.00905

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00702

Hom.:

Bravo

AF:

0.00503

Asia WGS

AF:

0.00173

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 20, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	TBK1: BP4, BS2 -

Frontotemporal dementia and/or amyotrophic lateral sclerosis 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

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