rs7985912
Variant names:
Variant summary
Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_014832.5(TBC1D4):c.3317-254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,984 control chromosomes in the GnomAD database, including 7,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.29 ( 7755 hom., cov: 31)
Consequence
TBC1D4
NM_014832.5 intron
NM_014832.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.53
Publications
0 publications found
Genes affected
TBC1D4 (HGNC:19165): (TBC1 domain family member 4) This gene is a member of the Tre-2/BUB2/CDC16 domain family. The protein encoded by this gene is a Rab-GTPase-activating protein, and contains two phopshotyrosine-binding domains (PTB1 and PTB2), a calmodulin-binding domain (CBD), a Rab-GTPase domain, and multiple AKT phosphomotifs. This protein is thought to play an important role in glucose homeostasis by regulating the insulin-dependent trafficking of the glucose transporter 4 (GLUT4), important for removing glucose from the bloodstream into skeletal muscle and fat tissues. Reduced expression of this gene results in an increase in GLUT4 levels at the plasma membrane, suggesting that this protein is important in intracellular retention of GLUT4 under basal conditions. When exposed to insulin, this protein is phosphorylated, dissociates from GLUT4 vesicles, resulting in increased GLUT4 at the cell surface, and enhanced glucose transport. Phosphorylation of this protein by AKT is required for proper translocation of GLUT4 to the cell surface. Individuals homozygous for a mutation in this gene are at higher risk for type 2 diabetes and have higher levels of circulating glucose and insulin levels after glucose ingestion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
Variant 13-75292525-C-T is Benign according to our data. Variant chr13-75292525-C-T is described in ClinVar as Benign. ClinVar VariationId is 1222510.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_014832.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TBC1D4 | NM_014832.5 | MANE Select | c.3317-254G>A | intron | N/A | NP_055647.2 | O60343-1 | ||
| TBC1D4 | NM_001286658.2 | c.3293-254G>A | intron | N/A | NP_001273587.1 | O60343-3 | |||
| TBC1D4 | NM_001286659.2 | c.3128-254G>A | intron | N/A | NP_001273588.1 | O60343-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TBC1D4 | ENST00000377636.8 | TSL:2 MANE Select | c.3317-254G>A | intron | N/A | ENSP00000366863.3 | O60343-1 | ||
| TBC1D4 | ENST00000431480.6 | TSL:1 | c.3293-254G>A | intron | N/A | ENSP00000395986.2 | O60343-3 | ||
| TBC1D4 | ENST00000377625.6 | TSL:1 | c.3128-254G>A | intron | N/A | ENSP00000366852.2 | O60343-2 |
Frequencies
GnomAD3 genomes 0.294 AC: 44598AN: 151864Hom.: 7727 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
44598
AN:
151864
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.294 AC: 44678AN: 151984Hom.: 7755 Cov.: 31 AF XY: 0.285 AC XY: 21156AN XY: 74264 show subpopulations
GnomAD4 genome
AF:
AC:
44678
AN:
151984
Hom.:
Cov.:
31
AF XY:
AC XY:
21156
AN XY:
74264
show subpopulations
African (AFR)
AF:
AC:
19838
AN:
41474
American (AMR)
AF:
AC:
3608
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
AC:
751
AN:
3464
East Asian (EAS)
AF:
AC:
64
AN:
5172
South Asian (SAS)
AF:
AC:
948
AN:
4816
European-Finnish (FIN)
AF:
AC:
1783
AN:
10518
Middle Eastern (MID)
AF:
AC:
69
AN:
294
European-Non Finnish (NFE)
AF:
AC:
16883
AN:
67958
Other (OTH)
AF:
AC:
575
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1509
3017
4526
6034
7543
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
432
864
1296
1728
2160
<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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
569
AN:
3452
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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