rs11178988

Variant names:

• chr12-71926651-C-T
• rs11178988
• ENST00000550746.5:c.*3447C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.86).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D15	ENST00000550746.5	c.*3447C>T		3_prime_UTR_variant	Exon 18 of 18	1		ENSP00000448182.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

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) AC: 0 AN: 0

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

African (AFR) AF: 0.125 AC: 5206 AN: 41484

American (AMR) AF: 0.0825 AC: 1261 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3470

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

South Asian (SAS) AF: 0.110 AC: 529 AN: 4812

European-Finnish (FIN) AF: 0.0742 AC: 785 AN: 10580

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

European-Non Finnish (NFE) AF: 0.0667 AC: 4536 AN: 67990

Other (OTH) AF: 0.0848 AC: 179 AN: 2110

Alfa AF: 0.0723 Hom.: 264

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
PhyloP100		-0.22
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: rs11178988; hg19: chr12-72320431;