rs10009706

Positions:

• chr4-38077854-A-G

Variant summary

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

The NM_001396959.1(TBC1D1):​c.2333-12078A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,796 control chromosomes in the GnomAD database, including 9,089 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 0.33 (9089 hom., cov: 30)
• Consequence: TBC1D1 NM_001396959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D1	NM_001396959.1	c.2333-12078A>G		intron_variant		ENST00000698857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D1	ENST00000698857.1	c.2333-12078A>G		intron_variant			NM_001396959.1	A2

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50052 AN: 151678 Hom.: 9053 Cov.: 30

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.330 AC: 50132 AN: 151796 Hom.: 9089 Cov.: 30 AF XY: 0.329 AC XY: 24387 AN XY: 74164

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.311

Alfa AF: 0.286 Hom.: 6126

Bravo AF: 0.341

Asia WGS AF: 0.508 AC: 1768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.71
DANN	Benign	0.26

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: rs10009706; hg19: chr4-38079475;