dbSNP rs73985186: TBKBP1:c.634+10C>T (chr17-47698785-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001394755.1(TBKBP1):c.634+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,538,430 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 17 hom., cov: 31)

Exomes 𝑓: 0.00088 ( 14 hom. )

Consequence

TBKBP1
NM_001394755.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.759

Publications

1 publications found

Variant links:

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]

TBKBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 17-47698785-C-T is Benign according to our data. Variant chr17-47698785-C-T is described in ClinVar as Benign. ClinVar VariationId is 717513.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00776 (1180/152132) while in subpopulation AFR AF = 0.0273 (1131/41476). AF 95% confidence interval is 0.0259. There are 17 homozygotes in GnomAd4. There are 546 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBKBP1	NM_001394755.1	MANE Select	c.634+10C>T	intron	N/A	NP_001381684.1	A7MCY6-1
TBKBP1	NM_001394756.1		c.634+10C>T	intron	N/A	NP_001381685.1	A7MCY6-1
TBKBP1	NM_014726.2		c.634+10C>T	intron	N/A	NP_055541.1	A7MCY6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBKBP1	ENST00000578982.6	TSL:3 MANE Select	c.634+10C>T	intron	N/A	ENSP00000462339.2	A7MCY6-1
TBKBP1	ENST00000361722.7	TSL:1	c.634+10C>T	intron	N/A	ENSP00000354777.3	A7MCY6-1
TBKBP1	ENST00000851181.1		c.634+10C>T	intron	N/A	ENSP00000521240.1

Frequencies

GnomAD3 genomes

AF:

0.00774

AC:

1176

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0272

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00479

GnomAD2 exomes

AF:

0.00236

AC:

446

AN:

189266

AF XY:

0.00167

show subpopulations

Gnomad AFR exome

AF:

0.0275

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.000192

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000181

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.000881

AC:

1221

AN:

1386298

Hom.:

Cov.:

AF XY:

0.000760

AC XY:

517

AN XY:

680194

show subpopulations

African (AFR)

AF:

0.0290

AC:

912

AN:

31474

American (AMR)

AF:

0.00179

AC:

AN:

35694

Ashkenazi Jewish (ASJ)

AF:

0.000137

AC:

AN:

21900

East Asian (EAS)

AF:

0.00

AC:

AN:

37948

South Asian (SAS)

AF:

0.000146

AC:

AN:

75192

European-Finnish (FIN)

AF:

0.0000587

AC:

AN:

51078

Middle Eastern (MID)

AF:

0.00129

AC:

AN:

5418

European-Non Finnish (NFE)

AF:

0.0000944

AC:

101

AN:

1070474

Other (OTH)

AF:

0.00210

AC:

120

AN:

57120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

120

180

240

300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00776

AC:

1180

AN:

152132

Hom.:

Cov.:

AF XY:

0.00734

AC XY:

546

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0273

AC:

1131

AN:

41476

American (AMR)

AF:

0.00144

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

67990

Other (OTH)

AF:

0.00474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

118

178

237

296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00579

Hom.:

Bravo

AF:

0.00908

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

0.76

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over