rs6851312

Variant names:

• chr4-174247002-A-G
• rs6851312
• NM_012180.3:c.457-5784T>C

Variant summary

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

The NM_012180.3(FBXO8):​c.457-5784T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,844 control chromosomes in the GnomAD database, including 7,910 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 0.31 (7910 hom., cov: 32)
• Consequence: FBXO8 NM_012180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 5 publications found

Genes affected

FBXO8 (HGNC:13587): (F-box protein 8) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. It contains a C-terminal amino acid sequence that bears a significant similarity with a portion of yeast Sec7p, a critical regulator of vesicular protein transport. This human protein may interact with ADP-ribosylation factor(s)(ARFs) and exhibit ARF-GEF (guanine nucleotide exchange factor) activity. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012180.3. 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
	FBXO8	NM_012180.3	MANE Select	c.457-5784T>C		intron	N/A	NP_036312.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO8	ENST00000393674.7	TSL:1 MANE Select	c.457-5784T>C		intron	N/A	ENSP00000377280.2	Q9NRD0-1
	FBXO8	ENST00000503293.5	TSL:1	c.334-5784T>C		intron	N/A	ENSP00000422905.1	Q9NRD0-2
	FBXO8	ENST00000615392.4	TSL:1	c.334-5784T>C		intron	N/A	ENSP00000484517.1	Q9NRD0-2

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47333 AN: 151726 Hom.: 7906 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.312 AC: 47353 AN: 151844 Hom.: 7910 Cov.: 32 AF XY: 0.307 AC XY: 22756 AN XY: 74218

African (AFR) AF: 0.277 AC: 11460 AN: 41426

American (AMR) AF: 0.261 AC: 3968 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3468

East Asian (EAS) AF: 0.0187 AC: 97 AN: 5178

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4822

European-Finnish (FIN) AF: 0.366 AC: 3863 AN: 10562

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24877 AN: 67884

Other (OTH) AF: 0.322 AC: 676 AN: 2102

Alfa AF: 0.349 Hom.: 27864

Bravo AF: 0.303

Asia WGS AF: 0.132 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.70
PhyloP100		0.21
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: rs6851312; hg19: chr4-175168153;