2-101113826-C-T

Position:

• chr2-101113826-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.128-23462G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,046 control chromosomes in the GnomAD database, including 31,027 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 0.64 (31027 hom., cov: 32)
• Consequence: TBC1D8 NM_001330348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D8	NM_001330348.2	c.128-23462G>A		intron_variant		ENST00000409318.2	NP_001317277.1
TBC1D8	NM_001102426.3	c.128-23462G>A		intron_variant			NP_001095896.1
TBC1D8	NR_138475.2	n.257-23462G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D8	ENST00000409318.2	c.128-23462G>A		intron_variant		5	NM_001330348.2	ENSP00000386856	A1
TBC1D8	ENST00000376840.8	c.128-23462G>A		intron_variant		1		ENSP00000366036	P4
TBC1D8	ENST00000463469.5	n.450-23462G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96779 AN: 151928 Hom.: 30984 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.637 AC: 96884 AN: 152046 Hom.: 31027 Cov.: 32 AF XY: 0.640 AC XY: 47571 AN XY: 74314

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.804

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.623

Alfa AF: 0.611 Hom.: 58934

Bravo AF: 0.636

Asia WGS AF: 0.703 AC: 2445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.039
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6543018; hg19: chr2-101730288;