rs9999507

Variant names:

• chr4-37999551-A-G
• rs9999507
• NM_001396959.1:c.418-14958A>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.418-14958A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 151,762 control chromosomes in the GnomAD database, including 27,090 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 0.59 (27090 hom., cov: 30)
• Consequence: TBC1D1 NM_001396959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 1 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):

• non-syndromic renal or urinary tract malformation

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D1	NM_001396959.1	MANE Select	c.418-14958A>G		intron	N/A	NP_001383888.1	A0A8V8TNS9
	TBC1D1	NM_015173.4		c.418-14958A>G		intron	N/A	NP_055988.2
	TBC1D1	NM_001253912.2		c.418-14958A>G		intron	N/A	NP_001240841.1	Q86TI0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D1	ENST00000698857.1	MANE Select	c.418-14958A>G		intron	N/A	ENSP00000513987.1	A0A8V8TNS9
	TBC1D1	ENST00000261439.9	TSL:1	c.418-14958A>G		intron	N/A	ENSP00000261439.4	Q86TI0-1
	TBC1D1	ENST00000961338.1		c.418-14958A>G		intron	N/A	ENSP00000631397.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88908 AN: 151644 Hom.: 27066 Cov.: 30

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.586 AC: 88985 AN: 151762 Hom.: 27090 Cov.: 30 AF XY: 0.589 AC XY: 43681 AN XY: 74152

African (AFR) AF: 0.710 AC: 29389 AN: 41374

American (AMR) AF: 0.630 AC: 9606 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1946 AN: 3468

East Asian (EAS) AF: 0.890 AC: 4567 AN: 5132

South Asian (SAS) AF: 0.600 AC: 2881 AN: 4802

European-Finnish (FIN) AF: 0.459 AC: 4829 AN: 10522

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33830 AN: 67898

Other (OTH) AF: 0.584 AC: 1229 AN: 2104

Alfa AF: 0.544 Hom.: 2847

Bravo AF: 0.608

Asia WGS AF: 0.762 AC: 2649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		-0.66
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: rs9999507; hg19: chr4-38001172;