rs11686264

Variant names:

• chr2-101133461-A-G
• rs11686264
• NM_001330348.2:c.127+17666T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001330348.2(TBC1D8):​c.127+17666T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 152,074 control chromosomes in the GnomAD database, including 129 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 0.034 (129 hom., cov: 31)
• Consequence: TBC1D8 NM_001330348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• Publications: 2 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=-0.93).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0345 (5245/152074) while in subpopulation NFE AF = 0.0491 (3336/67978). AF 95% confidence interval is 0.0477. There are 129 homozygotes in GnomAd4. There are 2594 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 129 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D8	NM_001330348.2	c.127+17666T>C		intron_variant	Intron 1 of 19	ENST00000409318.2	NP_001317277.1
TBC1D8	NM_001102426.3	c.127+17666T>C		intron_variant	Intron 1 of 19		NP_001095896.1
TBC1D8	NR_138475.2	n.256+17666T>C		intron_variant	Intron 1 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D8	ENST00000409318.2	c.127+17666T>C		intron_variant	Intron 1 of 19	5	NM_001330348.2	ENSP00000386856.1
TBC1D8	ENST00000376840.8	c.127+17666T>C		intron_variant	Intron 1 of 19	1		ENSP00000366036.4
TBC1D8	ENST00000463469.5	n.450-43097T>C		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5247 AN: 151956 Hom.: 130 Cov.: 31

Gnomad AFR AF: 0.00938

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.0479

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0277

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.0412

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

GnomAD4 genome AF: 0.0345 AC: 5245 AN: 152074 Hom.: 129 Cov.: 31 AF XY: 0.0349 AC XY: 2594 AN XY: 74348

African (AFR) AF: 0.00935 AC: 388 AN: 41500

American (AMR) AF: 0.0478 AC: 730 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 164 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

South Asian (SAS) AF: 0.0281 AC: 135 AN: 4806

European-Finnish (FIN) AF: 0.0304 AC: 322 AN: 10576

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0491 AC: 3336 AN: 67978

Other (OTH) AF: 0.0408 AC: 86 AN: 2108

Alfa AF: 0.0429 Hom.: 68

Bravo AF: 0.0332

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.67
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism

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: rs11686264; hg19: chr2-101749923;