rs2303422

Positions:

• chr4-38090179-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173

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=-0.82).
• 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
TBC1D1	NM_001396959.1	c.2518+62A>G		intron_variant		ENST00000698857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D1	ENST00000698857.1	c.2518+62A>G		intron_variant			NM_001396959.1	A2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19916 AN: 152202 Hom.: 1821 Cov.: 33

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

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

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

Other links and lift over

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