Genetic Variant TBC1D1:c.2073-145A>G (chr4-38052961-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001396959.1(TBC1D1):c.2073-145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 482,726 control chromosomes in the GnomAD database, including 70,746 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 0.57 ( 25876 hom., cov: 33)

Exomes 𝑓: 0.51 ( 44870 hom. )

Consequence

TBC1D1
NM_001396959.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

Publications

4 publications found

Variant links:

Genes affected

TBC1D1 (HGNC:11578): (TBC1 domain family member 1) TBC1D1 is the founding member of a family of proteins sharing a 180- to 200-amino acid TBC domain presumed to have a role in regulating cell growth and differentiation. These proteins share significant homology with TRE2 (USP6; MIM 604334), yeast Bub2, and CDC16 (MIM 603461) (White et al., 2000 [PubMed 10965142]).[supplied by OMIM, Mar 2008]

TBC1D1 Gene-Disease associations (from GenCC):

non-syndromic renal or urinary tract malformation
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
congenital anomaly of kidney and urinary tract
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

TBC1D1 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396959.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBC1D1	NM_001396959.1	MANE Select	c.2073-145A>G	intron	N/A	NP_001383888.1	A0A8V8TNS9
TBC1D1	NM_015173.4		c.1911-1238A>G	intron	N/A	NP_055988.2
TBC1D1	NM_001253912.2		c.2073-145A>G	intron	N/A	NP_001240841.1	Q86TI0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBC1D1	ENST00000698857.1	MANE Select	c.2073-145A>G	intron	N/A	ENSP00000513987.1	A0A8V8TNS9
TBC1D1	ENST00000261439.9	TSL:1	c.1911-1238A>G	intron	N/A	ENSP00000261439.4	Q86TI0-1
TBC1D1	ENST00000961338.1		c.2073-145A>G	intron	N/A	ENSP00000631397.1

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

86732

AN:

151972

Hom.:

25819

Cov.:

show subpopulations

Gnomad AFR

AF:

0.750

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.548

Gnomad EAS

AF:

0.665

Gnomad SAS

AF:

0.545

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.541

GnomAD4 exome

AF:

0.514

AC:

169940

AN:

330636

Hom.:

44870

AF XY:

0.513

AC XY:

84793

AN XY:

165448

show subpopulations

African (AFR)

AF:

0.752

AC:

6240

AN:

8294

American (AMR)

AF:

0.460

AC:

3158

AN:

6868

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

4740

AN:

9020

East Asian (EAS)

AF:

0.697

AC:

14763

AN:

21194

South Asian (SAS)

AF:

0.554

AC:

2266

AN:

4092

European-Finnish (FIN)

AF:

0.466

AC:

14226

AN:

30534

Middle Eastern (MID)

AF:

0.499

AC:

694

AN:

1390

European-Non Finnish (NFE)

AF:

0.494

AC:

114221

AN:

231058

Other (OTH)

AF:

0.530

AC:

9632

AN:

18186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3816

7632

11448

15264

19080

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1998

3996

5994

7992

9990

<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:

0.571

AC:

86841

AN:

152090

Hom.:

25876

Cov.:

AF XY:

0.566

AC XY:

42064

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.750

AC:

31145

AN:

41504

American (AMR)

AF:

0.455

AC:

6952

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.548

AC:

1902

AN:

3468

East Asian (EAS)

AF:

0.665

AC:

3448

AN:

5182

South Asian (SAS)

AF:

0.543

AC:

2619

AN:

4822

European-Finnish (FIN)

AF:

0.472

AC:

4976

AN:

10550

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.500

AC:

33992

AN:

67972

Other (OTH)

AF:

0.546

AC:

1153

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1860

3721

5581

7442

9302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<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:

0.548

Hom.:

3073

Bravo

AF:

0.578

Asia WGS

AF:

0.638

AC:

2219

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.4

(source)

DANN

Benign

0.41

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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