rs10517456

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TBC1D1	NM_001396959.1	c.417+50599G>A		intron_variant		ENST00000698857.1	NP_001383888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D1	ENST00000698857.1	c.417+50599G>A		intron_variant			NM_001396959.1	ENSP00000513987	A2
TBC1D1	ENST00000261439.9	c.417+50599G>A		intron_variant		1		ENSP00000261439	P2
TBC1D1	ENST00000508802.5	c.417+50599G>A		intron_variant		2		ENSP00000423651
TBC1D1	ENST00000698858.1	n.466+42751G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.625

Alfa AF: 0.597 Hom.: 9689

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10517456; hg19: chr4-37954732;