chr4-38124477-A-T

Position:

• chr4-38124477-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001396959.1(TBC1D1):​c.3245-485A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,182 control chromosomes in the GnomAD database, including 37,273 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 0.70 (37273 hom., cov: 34)
• Consequence: TBC1D1 NM_001396959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D1	NM_001396959.1	c.3245-485A>T		intron_variant		ENST00000698857.1	NP_001383888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D1	ENST00000698857.1	c.3245-485A>T		intron_variant			NM_001396959.1	ENSP00000513987.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106191 AN: 152064 Hom.: 37238 Cov.: 34

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.698 AC: 106285 AN: 152182 Hom.: 37273 Cov.: 34 AF XY: 0.693 AC XY: 51538 AN XY: 74390

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.713

Alfa AF: 0.618 Hom.: 1721

Bravo AF: 0.709

Asia WGS AF: 0.719 AC: 2499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.40

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: rs637797; hg19: chr4-38126098;