rs6823014

Variant names:

• chr4-38052961-A-G
• rs6823014
• NM_001396959.1:c.2073-145A>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.2073-145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 482,726 control chromosomes in the GnomAD database, including 70,746 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 0.57 (25876 hom., cov: 33)
  • Exomes 𝑓: 0.51 (44870 hom.)
• Consequence: TBC1D1 NM_001396959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D1	NM_001396959.1	c.2073-145A>G		intron_variant	Intron 12 of 21	ENST00000698857.1	NP_001383888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D1	ENST00000698857.1	c.2073-145A>G		intron_variant	Intron 12 of 21		NM_001396959.1	ENSP00000513987.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86732 AN: 151972 Hom.: 25819 Cov.: 33

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.541

GnomAD4 exome AF: 0.514 AC: 169940 AN: 330636 Hom.: 44870 AF XY: 0.513 AC XY: 84793 AN XY: 165448

African (AFR) AF: 0.752 AC: 6240 AN: 8294

American (AMR) AF: 0.460 AC: 3158 AN: 6868

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 4740 AN: 9020

East Asian (EAS) AF: 0.697 AC: 14763 AN: 21194

South Asian (SAS) AF: 0.554 AC: 2266 AN: 4092

European-Finnish (FIN) AF: 0.466 AC: 14226 AN: 30534

Middle Eastern (MID) AF: 0.499 AC: 694 AN: 1390

European-Non Finnish (NFE) AF: 0.494 AC: 114221 AN: 231058

Other (OTH) AF: 0.530 AC: 9632 AN: 18186

GnomAD4 genome AF: 0.571 AC: 86841 AN: 152090 Hom.: 25876 Cov.: 33 AF XY: 0.566 AC XY: 42064 AN XY: 74370

African (AFR) AF: 0.750 AC: 31145 AN: 41504

American (AMR) AF: 0.455 AC: 6952 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1902 AN: 3468

East Asian (EAS) AF: 0.665 AC: 3448 AN: 5182

South Asian (SAS) AF: 0.543 AC: 2619 AN: 4822

European-Finnish (FIN) AF: 0.472 AC: 4976 AN: 10550

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33992 AN: 67972

Other (OTH) AF: 0.546 AC: 1153 AN: 2110

Alfa AF: 0.548 Hom.: 3073

Bravo AF: 0.578

Asia WGS AF: 0.638 AC: 2219 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.41
PhyloP100		1.1
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: rs6823014; hg19: chr4-38054582;