chr4-38132364-T-C

Variant names:

• chr4-38132364-T-C
• rs6837834
• NM_001396959.1:c.3415-720T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

TBC1D1 Gene-Disease associations (from GenCC):

• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TBC1D1	NM_001396959.1	c.3415-720T>C		intron_variant	Intron 20 of 21	ENST00000698857.1	NP_001383888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D1	ENST00000698857.1	c.3415-720T>C		intron_variant	Intron 20 of 21		NM_001396959.1	ENSP00000513987.1

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

African (AFR) AF: 0.170 AC: 7071 AN: 41538

American (AMR) AF: 0.145 AC: 2215 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 678 AN: 3470

East Asian (EAS) AF: 0.352 AC: 1822 AN: 5174

South Asian (SAS) AF: 0.216 AC: 1041 AN: 4822

European-Finnish (FIN) AF: 0.0748 AC: 794 AN: 10616

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8519 AN: 68018

Other (OTH) AF: 0.168 AC: 355 AN: 2108

Alfa AF: 0.0993 Hom.: 249

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
PhyloP100		0.057
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6837834; hg19: chr4-38133985;