chr17-47698964-T-G

Variant names:

• chr17-47698964-T-G
• rs9913503
• NM_001394755.1:c.634+189T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394755.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBKBP1	NM_001394755.1	MANE Select	c.634+189T>G		intron	N/A	NP_001381684.1
	TBKBP1	NM_001394756.1		c.634+189T>G		intron	N/A	NP_001381685.1
	TBKBP1	NM_014726.2		c.634+189T>G		intron	N/A	NP_055541.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBKBP1	ENST00000578982.6	TSL:3 MANE Select	c.634+189T>G		intron	N/A	ENSP00000462339.2
	TBKBP1	ENST00000361722.7	TSL:1	c.634+189T>G		intron	N/A	ENSP00000354777.3
	TBKBP1	ENST00000537587.6	TSL:3	c.*197T>G		downstream_gene	N/A	ENSP00000446365.2

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

African (AFR) AF: 0.829 AC: 34321 AN: 41378

American (AMR) AF: 0.546 AC: 8332 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2321 AN: 3470

East Asian (EAS) AF: 0.611 AC: 3139 AN: 5138

South Asian (SAS) AF: 0.564 AC: 2705 AN: 4796

European-Finnish (FIN) AF: 0.513 AC: 5390 AN: 10512

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40207 AN: 67890

Other (OTH) AF: 0.640 AC: 1346 AN: 2104

Alfa AF: 0.606 Hom.: 12184

Bravo AF: 0.660

Asia WGS AF: 0.521 AC: 1816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.36
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9913503; hg19: chr17-45776330;