rs6845120

Positions:

• chr4-38045924-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.1629+21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,603,316 control chromosomes in the GnomAD database, including 80,386 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 0.32 (8224 hom., cov: 32)
  • Exomes 𝑓: 0.31 (72162 hom.)
• Consequence: TBC1D1 NM_001396959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D1	NM_001396959.1	c.1629+21A>G		intron_variant		ENST00000698857.1	NP_001383888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D1	ENST00000698857.1	c.1629+21A>G		intron_variant			NM_001396959.1	ENSP00000513987	A2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48648 AN: 151854 Hom.: 8217 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.302

GnomAD3 exomes AF: 0.327 AC: 82140 AN: 251080 Hom.: 14537 AF XY: 0.326 AC XY: 44223 AN XY: 135736

Gnomad AFR exome AF: 0.356

Gnomad AMR exome AF: 0.299

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.614

Gnomad SAS exome AF: 0.365

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.292

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.307 AC: 446250 AN: 1451344 Hom.: 72162 Cov.: 27 AF XY: 0.308 AC XY: 222423 AN XY: 722754

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.298

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.654

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.320 AC: 48685 AN: 151972 Hom.: 8224 Cov.: 32 AF XY: 0.317 AC XY: 23543 AN XY: 74276

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.304

Alfa AF: 0.301 Hom.: 4299

Bravo AF: 0.329

Asia WGS AF: 0.486 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.58
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6845120; hg19: chr4-38047545; COSMIC: COSV54719586; COSMIC: COSV54719586;