chr12-71899386-T-C

Position:

• chr12-71899386-T-C

Variant summary

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

The NM_001146213.3(TBC1D15):​c.1183+1445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,196 control chromosomes in the GnomAD database, including 3,635 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 0.18 (3635 hom., cov: 32)
• Consequence: TBC1D15 NM_001146213.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D15	NM_001146213.3	c.1183+1445T>C		intron_variant		ENST00000485960.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D15	ENST00000485960.7	c.1183+1445T>C		intron_variant		1	NM_001146213.3	P3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26644 AN: 152078 Hom.: 3621 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0417

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0971

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.175 AC: 26697 AN: 152196 Hom.: 3635 Cov.: 32 AF XY: 0.173 AC XY: 12873 AN XY: 74434

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0418

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.0971

Gnomad4 OTH AF: 0.153

Alfa AF: 0.102 Hom.: 1335

Bravo AF: 0.183

Asia WGS AF: 0.133 AC: 463 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs6582065; hg19: chr12-72293166;