rs11178988

chr12-71926651-C-T

Variant summary

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

The ENST00000550746.5(TBC1D15):c.*3447C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 152,116 control chromosomes in the GnomAD database, including 681 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 0.089 (681 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D15 ENST00000550746.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

Genes affected

TBC1D15 (HGNC:25694): (TBC1 domain family member 15) This gene encodes a member of the Ras-like proteins in brain-GTPase activating protein superfamily that share a conserved Tre-2/Bub2/Cdc16 domain. The encoded protein interacts with Ras-like protein in brain 5A and may function as a regulator of intracellular trafficking. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -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 = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D15	ENST00000550746.5	c.*3447C>T		3_prime_UTR_variant	18/18	1		A1

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13474 AN: 151998 Hom.: 677 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0816

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0667

Gnomad OTH AF: 0.0814

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 ASJ exome AF: 0.00

GnomAD4 genome AF: 0.0888 AC: 13503 AN: 152116 Hom.: 681 Cov.: 32 AF XY: 0.0901 AC XY: 6697 AN XY: 74360

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0825

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0742

Gnomad4 NFE AF: 0.0667

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.0722 Hom.: 230

Bravo AF: 0.0905

Asia WGS AF: 0.155 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.44
Dann	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11178988; hg19: chr12-72320431;