rs10517456

Variant names:

• chr4-37953111-G-A
• rs10517456
• NM_001396959.1:c.417+50599G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-37953111-G-A
• chr4-37953111-G-C
• chr4-37953111-G-T

Variant summary

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

The NM_001396959.1(TBC1D1):​c.417+50599G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,110 control chromosomes in the GnomAD database, including 30,280 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 0.62 (30280 hom., cov: 33)
• Consequence: TBC1D1 NM_001396959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D1	NM_001396959.1	c.417+50599G>A		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.417+50599G>A		intron_variant	Intron 2 of 21		NM_001396959.1	ENSP00000513987.1
TBC1D1	ENST00000261439.9	c.417+50599G>A		intron_variant	Intron 2 of 19	1		ENSP00000261439.4
TBC1D1	ENST00000508802.5	c.417+50599G>A		intron_variant	Intron 2 of 20	2		ENSP00000423651.1
TBC1D1	ENST00000698858.1	n.466+42751G>A		intron_variant	Intron 1 of 20

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94511 AN: 151992 Hom.: 30219 Cov.: 33

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.622 AC: 94635 AN: 152110 Hom.: 30280 Cov.: 33 AF XY: 0.628 AC XY: 46717 AN XY: 74344

African (AFR) AF: 0.702 AC: 29160 AN: 41512

American (AMR) AF: 0.681 AC: 10405 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2012 AN: 3470

East Asian (EAS) AF: 0.956 AC: 4968 AN: 5194

South Asian (SAS) AF: 0.649 AC: 3132 AN: 4826

European-Finnish (FIN) AF: 0.585 AC: 6173 AN: 10548

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36958 AN: 67972

Other (OTH) AF: 0.625 AC: 1321 AN: 2114

Alfa AF: 0.595 Hom.: 11862

Bravo AF: 0.634

Asia WGS AF: 0.810 AC: 2814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.9
DANN	Benign	0.75
PhyloP100		0.48
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: rs10517456; hg19: chr4-37954732;