rs2309997

Positions:

• chr2-101128582-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.127+22545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,250 control chromosomes in the GnomAD database, including 1,441 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 0.13 (1441 hom., cov: 32)
• Consequence: TBC1D8 NM_001330348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D8	NM_001330348.2	c.127+22545G>A		intron_variant		ENST00000409318.2
TBC1D8	NM_001102426.3	c.127+22545G>A		intron_variant
TBC1D8	NR_138475.2	n.256+22545G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D8	ENST00000409318.2	c.127+22545G>A		intron_variant		5	NM_001330348.2	A1
TBC1D8	ENST00000376840.8	c.127+22545G>A		intron_variant		1		P4
TBC1D8	ENST00000463469.5	n.450-38218G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19762 AN: 152132 Hom.: 1440 Cov.: 32

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.130 AC: 19770 AN: 152250 Hom.: 1441 Cov.: 32 AF XY: 0.132 AC XY: 9853 AN XY: 74438

Gnomad4 AFR AF: 0.0790

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.135

Alfa AF: 0.124 Hom.: 151

Bravo AF: 0.132

Asia WGS AF: 0.209 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.6
DANN	Benign	0.78

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: rs2309997; hg19: chr2-101745044;