12-71926704-C-A

Variant names:

• chr12-71926704-C-A
• rs11178989
• ENST00000550746.5:c.*3500C>A

Variant summary

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

The ENST00000550746.5(TBC1D15):​c.*3500C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 152,130 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 0.097 (845 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: -0.172
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D15	ENST00000550746.5	c.*3500C>A		3_prime_UTR_variant	Exon 18 of 18	1		ENSP00000448182.1

Frequencies

GnomAD3 genomes AF: 0.0966 AC: 14688 AN: 152012 Hom.: 840 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0838

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0739

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0842

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0968 AC: 14732 AN: 152130 Hom.: 845 Cov.: 32 AF XY: 0.0979 AC XY: 7283 AN XY: 74364

African (AFR) AF: 0.154 AC: 6393 AN: 41474

American (AMR) AF: 0.0846 AC: 1294 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3468

East Asian (EAS) AF: 0.161 AC: 834 AN: 5182

South Asian (SAS) AF: 0.110 AC: 531 AN: 4814

European-Finnish (FIN) AF: 0.0739 AC: 781 AN: 10574

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0668 AC: 4541 AN: 68010

Other (OTH) AF: 0.0876 AC: 185 AN: 2112

Alfa AF: 0.0678 Hom.: 256

Bravo AF: 0.0998

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.66
DANN	Benign	0.79
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11178989; hg19: chr12-72320484;