17-47698964-T-G

Position:

• chr17-47698964-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394755.1(TBKBP1):​c.634+189T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,754 control chromosomes in the GnomAD database, including 33,176 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (33176 hom., cov: 29)
• Consequence: TBKBP1 NM_001394755.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

Genes affected

TBKBP1 (HGNC:30140): (TBK1 binding protein 1) TBKBP1 is an adaptor protein that binds to TBK1 (MIM 604834) and is part of the interaction network in the TNF (MIM 191160)/NFKB (see MIM 164011) pathway (Bouwmeester et al., 2004 [PubMed 14743216]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBKBP1	NM_001394755.1	c.634+189T>G		intron_variant		ENST00000578982.6	NP_001381684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBKBP1	ENST00000578982.6	c.634+189T>G		intron_variant		3	NM_001394755.1	ENSP00000462339	P1
TBKBP1	ENST00000361722.7	c.634+189T>G		intron_variant		1		ENSP00000354777	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98398 AN: 151636 Hom.: 33122 Cov.: 29

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.649 AC: 98504 AN: 151754 Hom.: 33176 Cov.: 29 AF XY: 0.642 AC XY: 47599 AN XY: 74120

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.640

Alfa AF: 0.605 Hom.: 10615

Bravo AF: 0.660

Asia WGS AF: 0.521 AC: 1816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs9913503; hg19: chr17-45776330;