rs6837834

chr4-38132364-T-Cchr4-38132364-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001396959.1(TBC1D1):c.3415-720T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,246 control chromosomes in the GnomAD database, including 1,922 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 0.15 (1922 hom., cov: 32)
• Consequence: TBC1D1 NM_001396959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D1	NM_001396959.1	c.3415-720T>C		intron_variant		ENST00000698857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D1	ENST00000698857.1	c.3415-720T>C		intron_variant			NM_001396959.1	A2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22585 AN: 152128 Hom.: 1916 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.148 AC: 22601 AN: 152246 Hom.: 1922 Cov.: 32 AF XY: 0.148 AC XY: 11007 AN XY: 74442

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.0748

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.168

Alfa AF: 0.0979 Hom.: 231

Bravo AF: 0.156

Asia WGS AF: 0.300 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.0
Dann	Benign	0.51

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

Other links and lift over

dbSNP: rs6837834; hg19: chr4-38133985;