rs6543012

Positions:

• chr2-101074539-C-A
• chr2-101074539-C-T

Variant summary

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

The NM_001330348.2(TBC1D8):​c.284-15000G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,266 control chromosomes in the GnomAD database, including 59,362 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 0.88 (59362 hom., cov: 33)
• Consequence: TBC1D8 NM_001330348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679

Genes affected

TBC1D8 (HGNC:17791): (TBC1 domain family member 8) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D8	NM_001330348.2	c.284-15000G>T		intron_variant		ENST00000409318.2	NP_001317277.1
TBC1D8	NM_001102426.3	c.239-15000G>T		intron_variant			NP_001095896.1
TBC1D8	NR_138475.2	n.368-15000G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D8	ENST00000409318.2	c.284-15000G>T		intron_variant		5	NM_001330348.2	ENSP00000386856.1
TBC1D8	ENST00000376840.8	c.239-15000G>T		intron_variant		1		ENSP00000366036.4
TBC1D8	ENST00000487392.1	n.286-15000G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133863 AN: 152148 Hom.: 59310 Cov.: 33

Gnomad AFR AF: 0.973

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.880 AC: 133967 AN: 152266 Hom.: 59362 Cov.: 33 AF XY: 0.874 AC XY: 65033 AN XY: 74442

Gnomad4 AFR AF: 0.973

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.885

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.862

Gnomad4 OTH AF: 0.882

Alfa AF: 0.872 Hom.: 47134

Bravo AF: 0.893

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.30

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: rs6543012; hg19: chr2-101691001;