rs17425670

Variant names:

• chr4-38057143-A-G
• rs17425670
• NM_001396959.1:c.2332+2805A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001396959.1(TBC1D1):​c.2332+2805A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,048 control chromosomes in the GnomAD database, including 2,213 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 0.16 (2213 hom., cov: 32)
• Consequence: TBC1D1 NM_001396959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396959.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D1	NM_001396959.1	MANE Select	c.2332+2805A>G		intron	N/A	NP_001383888.1
	TBC1D1	NM_015173.4		c.2050+2805A>G		intron	N/A	NP_055988.2
	TBC1D1	NM_001253912.2		c.2332+2805A>G		intron	N/A	NP_001240841.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D1	ENST00000698857.1	MANE Select	c.2332+2805A>G		intron	N/A	ENSP00000513987.1
	TBC1D1	ENST00000261439.9	TSL:1	c.2050+2805A>G		intron	N/A	ENSP00000261439.4
	TBC1D1	ENST00000508802.5	TSL:2	c.2332+2805A>G		intron	N/A	ENSP00000423651.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24839 AN: 151930 Hom.: 2209 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.164 AC: 24872 AN: 152048 Hom.: 2213 Cov.: 32 AF XY: 0.162 AC XY: 12056 AN XY: 74328

African (AFR) AF: 0.152 AC: 6287 AN: 41462

American (AMR) AF: 0.124 AC: 1895 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3470

East Asian (EAS) AF: 0.0350 AC: 181 AN: 5170

South Asian (SAS) AF: 0.103 AC: 498 AN: 4824

European-Finnish (FIN) AF: 0.211 AC: 2235 AN: 10572

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12682 AN: 67952

Other (OTH) AF: 0.162 AC: 341 AN: 2106

Alfa AF: 0.177 Hom.: 4137

Bravo AF: 0.156

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.41
DANN	Benign	0.60
PhyloP100		-0.21
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: rs17425670; hg19: chr4-38058764;