2-101114673-G-A

Variant names:

• chr2-101114673-G-A
• rs2165427
• NM_001330348.2:c.128-24309C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330348.2(TBC1D8):​c.128-24309C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,176 control chromosomes in the GnomAD database, including 1,669 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 0.14 (1669 hom., cov: 33)
• Consequence: TBC1D8 NM_001330348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D8	NM_001330348.2	MANE Select	c.128-24309C>T		intron	N/A	NP_001317277.1
	TBC1D8	NM_001102426.3		c.128-24309C>T		intron	N/A	NP_001095896.1
	TBC1D8	NR_138475.2		n.257-24309C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D8	ENST00000409318.2	TSL:5 MANE Select	c.128-24309C>T		intron	N/A	ENSP00000386856.1
	TBC1D8	ENST00000376840.8	TSL:1	c.128-24309C>T		intron	N/A	ENSP00000366036.4
	TBC1D8	ENST00000463469.5	TSL:4	n.450-24309C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20813 AN: 152058 Hom.: 1666 Cov.: 33

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.137 AC: 20826 AN: 152176 Hom.: 1669 Cov.: 33 AF XY: 0.138 AC XY: 10274 AN XY: 74400

African (AFR) AF: 0.0640 AC: 2656 AN: 41520

American (AMR) AF: 0.211 AC: 3229 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0838 AC: 291 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1374 AN: 5168

South Asian (SAS) AF: 0.189 AC: 913 AN: 4826

European-Finnish (FIN) AF: 0.141 AC: 1492 AN: 10580

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10499 AN: 68006

Other (OTH) AF: 0.121 AC: 255 AN: 2108

Alfa AF: 0.144 Hom.: 2839

Bravo AF: 0.138

Asia WGS AF: 0.228 AC: 792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.67
PhyloP100		-0.37
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: rs2165427; hg19: chr2-101731135; COSMIC: COSV65211047; COSMIC: COSV65211047;