2-101113826-C-T

Variant names:

• chr2-101113826-C-T
• rs6543018
• NM_001330348.2:c.128-23462G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330348.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D8	NM_001330348.2	MANE Select	c.128-23462G>A		intron	N/A	NP_001317277.1	J3KQ40
	TBC1D8	NM_001102426.3		c.128-23462G>A		intron	N/A	NP_001095896.1	O95759-1
	TBC1D8	NR_138475.2		n.257-23462G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D8	ENST00000409318.2	TSL:5 MANE Select	c.128-23462G>A		intron	N/A	ENSP00000386856.1	J3KQ40
	TBC1D8	ENST00000376840.8	TSL:1	c.128-23462G>A		intron	N/A	ENSP00000366036.4	O95759-1
	TBC1D8	ENST00000870702.1		c.128-23462G>A		intron	N/A	ENSP00000540761.1

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

African (AFR) AF: 0.657 AC: 27258 AN: 41458

American (AMR) AF: 0.642 AC: 9807 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1653 AN: 3466

East Asian (EAS) AF: 0.804 AC: 4151 AN: 5160

South Asian (SAS) AF: 0.607 AC: 2928 AN: 4820

European-Finnish (FIN) AF: 0.675 AC: 7127 AN: 10562

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41935 AN: 67982

Other (OTH) AF: 0.623 AC: 1313 AN: 2106

Alfa AF: 0.616 Hom.: 91696

Bravo AF: 0.636

Asia WGS AF: 0.703 AC: 2445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.039
DANN	Benign	0.62
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6543018; hg19: chr2-101730288;