chr12-64455974-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_013254.4(TBK1):c.87+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,555,346 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 1 hom. )
Consequence
TBK1
NM_013254.4 intron
NM_013254.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.544
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 12-64455974-C-T is Benign according to our data. Variant chr12-64455974-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1983262.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000105 (16/152194) while in subpopulation EAS AF= 0.000192 (1/5200). AF 95% confidence interval is 0.0000905. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBK1 | NM_013254.4 | c.87+17C>T | intron_variant | ENST00000331710.10 | |||
TBK1 | XM_005268809.2 | c.87+17C>T | intron_variant | ||||
TBK1 | XM_005268810.2 | c.87+17C>T | intron_variant | ||||
TBK1 | XR_007063071.1 | n.186+17C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBK1 | ENST00000331710.10 | c.87+17C>T | intron_variant | 1 | NM_013254.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000109 AC: 25AN: 228804Hom.: 0 AF XY: 0.0000727 AC XY: 9AN XY: 123762
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GnomAD4 exome AF: 0.000231 AC: 324AN: 1403152Hom.: 1 Cov.: 25 AF XY: 0.000233 AC XY: 163AN XY: 700336
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at