rs2303422

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001396959.1(TBC1D1):​c.2518+62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,502,552 control chromosomes in the GnomAD database, including 21,720 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 0.13 ( 1823 hom., cov: 33)
Exomes 𝑓: 0.16 ( 19897 hom. )

Consequence

TBC1D1
NM_001396959.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.173
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TBC1D1NM_001396959.1 linkuse as main transcriptc.2518+62A>G intron_variant ENST00000698857.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TBC1D1ENST00000698857.1 linkuse as main transcriptc.2518+62A>G intron_variant NM_001396959.1 A2

Frequencies

GnomAD3 genomes
AF:
0.131
AC:
19916
AN:
152202
Hom.:
1821
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0286
Gnomad AMI
AF:
0.0691
Gnomad AMR
AF:
0.171
Gnomad ASJ
AF:
0.208
Gnomad EAS
AF:
0.417
Gnomad SAS
AF:
0.220
Gnomad FIN
AF:
0.134
Gnomad MID
AF:
0.0886
Gnomad NFE
AF:
0.152
Gnomad OTH
AF:
0.136
GnomAD4 exome
AF:
0.161
AC:
217004
AN:
1350232
Hom.:
19897
AF XY:
0.162
AC XY:
109725
AN XY:
677442
show subpopulations
Gnomad4 AFR exome
AF:
0.0232
Gnomad4 AMR exome
AF:
0.200
Gnomad4 ASJ exome
AF:
0.203
Gnomad4 EAS exome
AF:
0.419
Gnomad4 SAS exome
AF:
0.214
Gnomad4 FIN exome
AF:
0.124
Gnomad4 NFE exome
AF:
0.150
Gnomad4 OTH exome
AF:
0.166
GnomAD4 genome
AF:
0.131
AC:
19926
AN:
152320
Hom.:
1823
Cov.:
33
AF XY:
0.132
AC XY:
9813
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0285
Gnomad4 AMR
AF:
0.171
Gnomad4 ASJ
AF:
0.208
Gnomad4 EAS
AF:
0.418
Gnomad4 SAS
AF:
0.219
Gnomad4 FIN
AF:
0.134
Gnomad4 NFE
AF:
0.152
Gnomad4 OTH
AF:
0.138
Alfa
AF:
0.136
Hom.:
340
Bravo
AF:
0.132
Asia WGS
AF:
0.309
AC:
1074
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
5.9
DANN
Benign
0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2303422; hg19: chr4-38091800; COSMIC: COSV54715381; COSMIC: COSV54715381; API