chr12-71840169-G-A

Variant names:

• chr12-71840169-G-A
• rs328764
• NM_001146213.3:c.30+358G>A

Variant summary

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

The NM_001146213.3(TBC1D15):​c.30+358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,174 control chromosomes in the GnomAD database, including 3,265 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 0.20 (3265 hom., cov: 32)
• Consequence: TBC1D15 NM_001146213.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D15	NM_001146213.3	c.30+358G>A		intron_variant	Intron 1 of 16	ENST00000485960.7	NP_001139685.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D15	ENST00000485960.7	c.30+358G>A		intron_variant	Intron 1 of 16	1	NM_001146213.3	ENSP00000420678.2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29808 AN: 152056 Hom.: 3252 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.196 AC: 29853 AN: 152174 Hom.: 3265 Cov.: 32 AF XY: 0.196 AC XY: 14548 AN XY: 74410

African (AFR) AF: 0.276 AC: 11438 AN: 41510

American (AMR) AF: 0.136 AC: 2082 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3470

East Asian (EAS) AF: 0.102 AC: 528 AN: 5184

South Asian (SAS) AF: 0.302 AC: 1458 AN: 4820

European-Finnish (FIN) AF: 0.119 AC: 1259 AN: 10586

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11911 AN: 68004

Other (OTH) AF: 0.194 AC: 410 AN: 2112

Alfa AF: 0.187 Hom.: 716

Bravo AF: 0.196

Asia WGS AF: 0.250 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.072
DANN	Benign	0.80
PhyloP100		-2.0
PromoterAI		0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs328764; hg19: chr12-72233949;