chr12-71921202-T-C

Variant names:

• chr12-71921202-T-C
• rs17110426
• NM_001146213.3:c.1717-166T>C

Variant summary

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

The NM_001146213.3(TBC1D15):​c.1717-166T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 152,232 control chromosomes in the GnomAD database, including 685 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 (685 hom., cov: 33)
• Consequence: TBC1D15 NM_001146213.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432
• Publications: 4 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 = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146213.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D15	NM_001146213.3	MANE Select	c.1717-166T>C		intron	N/A	NP_001139685.2
	TBC1D15	NM_022771.6		c.1768-166T>C		intron	N/A	NP_073608.4
	TBC1D15	NM_001385848.1		c.1711-166T>C		intron	N/A	NP_001372777.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D15	ENST00000485960.7	TSL:1 MANE Select	c.1717-166T>C		intron	N/A	ENSP00000420678.2
	TBC1D15	ENST00000550746.5	TSL:1	c.1768-166T>C		intron	N/A	ENSP00000448182.1
	TBC1D15	ENST00000462788.6	TSL:1	n.*1131-166T>C		intron	N/A	ENSP00000418467.2

Frequencies

GnomAD3 genomes AF: 0.0890 AC: 13545 AN: 152114 Hom.: 681 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0822

Gnomad ASJ AF: 0.0332

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0735

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.0812

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

GnomAD4 genome AF: 0.0892 AC: 13574 AN: 152232 Hom.: 685 Cov.: 33 AF XY: 0.0905 AC XY: 6733 AN XY: 74436

African (AFR) AF: 0.126 AC: 5212 AN: 41526

American (AMR) AF: 0.0831 AC: 1271 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0332 AC: 115 AN: 3468

East Asian (EAS) AF: 0.163 AC: 848 AN: 5196

South Asian (SAS) AF: 0.113 AC: 547 AN: 4826

European-Finnish (FIN) AF: 0.0735 AC: 779 AN: 10592

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0671 AC: 4566 AN: 68000

Other (OTH) AF: 0.0846 AC: 179 AN: 2116

Alfa AF: 0.0578 Hom.: 183

Bravo AF: 0.0911

Asia WGS AF: 0.156 AC: 539 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.54
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17110426; hg19: chr12-72314982;