rs17110432

Positions:

• chr12-71925061-A-G

Variant summary

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

The ENST00000550746.5(TBC1D15):​c.*1857A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0964 in 151,688 control chromosomes in the GnomAD database, including 845 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 0.096 (845 hom., cov: 31)
  • 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: 1.31

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.71925061A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D15	ENST00000550746.5	c.*1857A>G		3_prime_UTR_variant	18/18	1		ENSP00000448182.1

Frequencies

GnomAD3 genomes AF: 0.0961 AC: 14572 AN: 151574 Hom.: 839 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.0849

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0964 AC: 14619 AN: 151688 Hom.: 845 Cov.: 31 AF XY: 0.0970 AC XY: 7193 AN XY: 74122

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0839

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0698

Gnomad4 NFE AF: 0.0672

Gnomad4 OTH AF: 0.0882

Alfa AF: 0.0821 Hom.: 76

Bravo AF: 0.101

Asia WGS AF: 0.162 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.5
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17110432; hg19: chr12-72318841;