Genetic Variant TBC1D9B:n.3245C>T (chr5-179862659-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000518085.1(TBC1D9B):n.3245C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 446,016 control chromosomes in the GnomAD database, including 6,627 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 0.098 ( 1269 hom., cov: 33)

Exomes 𝑓: 0.15 ( 5358 hom. )

Consequence

TBC1D9B
ENST00000518085.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.159

Publications

8 publications found

Variant links:

Genes affected

TBC1D9B (HGNC:29097): (TBC1 domain family member 9B) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D9B links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518085.1. 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
	TBC1D9B	NM_015043.4	MANE Select	c.*789C>T		3_prime_UTR	Exon 21 of 21	NP_055858.2
	TBC1D9B	NM_198868.3		c.*789C>T		3_prime_UTR	Exon 22 of 22	NP_942568.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TBC1D9B	ENST00000518085.1	TSL:1	n.3245C>T	non_coding_transcript_exon	Exon 2 of 2
TBC1D9B	ENST00000355235.8	TSL:5 MANE Select	c.*789C>T	3_prime_UTR	Exon 21 of 21	ENSP00000347375.3
TBC1D9B	ENST00000356834.7	TSL:1	c.*789C>T	3_prime_UTR	Exon 22 of 22	ENSP00000349291.3

Frequencies

GnomAD3 genomes

AF:

0.0979

AC:

14901

AN:

152138

Hom.:

1264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.0847

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0810

Gnomad OTH

AF:

0.0924

GnomAD4 exome

AF:

0.152

AC:

44610

AN:

293760

Hom.:

5358

Cov.:

AF XY:

0.159

AC XY:

26370

AN XY:

165496

show subpopulations

African (AFR)

AF:

0.0183

AC:

155

AN:

8468

American (AMR)

AF:

0.350

AC:

9489

AN:

27114

Ashkenazi Jewish (ASJ)

AF:

0.0873

AC:

934

AN:

10702

East Asian (EAS)

AF:

0.354

AC:

3160

AN:

8922

South Asian (SAS)

AF:

0.253

AC:

15084

AN:

59508

European-Finnish (FIN)

AF:

0.158

AC:

2003

AN:

12696

Middle Eastern (MID)

AF:

0.0935

AC:

257

AN:

2750

European-Non Finnish (NFE)

AF:

0.0795

AC:

11916

AN:

149926

Other (OTH)

AF:

0.118

AC:

1612

AN:

13674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1833

3665

5498

7330

9163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.0980

AC:

14914

AN:

152256

Hom.:

1269

Cov.:

AF XY:

0.108

AC XY:

8073

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0193

AC:

802

AN:

41564

American (AMR)

AF:

0.199

AC:

3038

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0847

AC:

294

AN:

3470

East Asian (EAS)

AF:

0.371

AC:

1917

AN:

5174

South Asian (SAS)

AF:

0.277

AC:

1335

AN:

4826

European-Finnish (FIN)

AF:

0.165

AC:

1750

AN:

10598

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0810

AC:

5509

AN:

68018

Other (OTH)

AF:

0.100

AC:

212

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

640

1279

1919

2558

3198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.0950

Hom.:

1299

Bravo

AF:

0.0986

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.2

(source)

DANN

Benign

0.58

PhyloP100

0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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