4-37965556-G-C

Variant names:

• chr4-37965556-G-C
• rs10517461
• NM_001396959.1:c.418-48953G>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.418-48953G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,764 control chromosomes in the GnomAD database, including 12,891 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 0.41 (12891 hom., cov: 30)
• Consequence: TBC1D1 NM_001396959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D1	NM_001396959.1	c.418-48953G>C		intron_variant	Intron 2 of 21	ENST00000698857.1	NP_001383888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D1	ENST00000698857.1	c.418-48953G>C		intron_variant	Intron 2 of 21		NM_001396959.1	ENSP00000513987.1
TBC1D1	ENST00000261439.9	c.418-48953G>C		intron_variant	Intron 2 of 19	1		ENSP00000261439.4
TBC1D1	ENST00000508802.5	c.418-48953G>C		intron_variant	Intron 2 of 20	2		ENSP00000423651.1
TBC1D1	ENST00000698858.1	n.467-48953G>C		intron_variant	Intron 1 of 20

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61547 AN: 151646 Hom.: 12856 Cov.: 30

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.406 AC: 61633 AN: 151764 Hom.: 12891 Cov.: 30 AF XY: 0.405 AC XY: 30050 AN XY: 74130

African (AFR) AF: 0.485 AC: 20067 AN: 41346

American (AMR) AF: 0.366 AC: 5571 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1791 AN: 3468

East Asian (EAS) AF: 0.510 AC: 2623 AN: 5146

South Asian (SAS) AF: 0.420 AC: 2021 AN: 4812

European-Finnish (FIN) AF: 0.352 AC: 3712 AN: 10538

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24646 AN: 67894

Other (OTH) AF: 0.426 AC: 900 AN: 2114

Alfa AF: 0.279 Hom.: 786

Bravo AF: 0.411

Asia WGS AF: 0.436 AC: 1515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.46
PhyloP100		-0.58
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: rs10517461; hg19: chr4-37967177;