rs371275822

Variant names:

• chr12-64497638-G-A
• NM_013254.4:c.1960-10G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-64497638-G-A
• chr12-64497638-G-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_013254.4(TBK1):​c.1960-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: TBK1 NM_013254.4 intron
• Scores: Splicing: ADA: 0.0003317
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 12-64497638-G-A is Benign according to our data. Variant chr12-64497638-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBK1	NM_013254.4	c.1960-10G>A		intron_variant	Intron 18 of 20	ENST00000331710.10	NP_037386.1
TBK1	XM_005268809.2	c.1960-10G>A		intron_variant	Intron 18 of 20		XP_005268866.1
TBK1	XM_005268810.2	c.1960-10G>A		intron_variant	Intron 18 of 20		XP_005268867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBK1	ENST00000331710.10	c.1960-10G>A		intron_variant	Intron 18 of 20	1	NM_013254.4	ENSP00000329967.5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000595 AC: 3 AN: 504286 Hom.: 0 Cov.: 17 AF XY: 0.0000119 AC XY: 3 AN XY: 252988

Gnomad4 AFR exome AF: 0.0000803

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000101

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000569

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.7
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00033
dbscSNV1_RF	Benign	0.024
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-64891418;