2-101133461-A-G

Position:

• chr2-101133461-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

TBC1D8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 129 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D8	NM_001330348.2	c.127+17666T>C		intron_variant		ENST00000409318.2	NP_001317277.1
TBC1D8	NM_001102426.3	c.127+17666T>C		intron_variant			NP_001095896.1
TBC1D8	NR_138475.2	n.256+17666T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D8	ENST00000409318.2	c.127+17666T>C		intron_variant		5	NM_001330348.2	ENSP00000386856.1
TBC1D8	ENST00000376840.8	c.127+17666T>C		intron_variant		1		ENSP00000366036.4
TBC1D8	ENST00000463469.5	n.450-43097T>C		intron_variant		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

Gnomad4 AFR AF: 0.00935

Gnomad4 AMR AF: 0.0478

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0281

Gnomad4 FIN AF: 0.0304

Gnomad4 NFE AF: 0.0491

Gnomad4 OTH AF: 0.0408

Alfa AF: 0.0428 Hom.: 60

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

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: rs11686264; hg19: chr2-101749923;