rs9479476

chr6-152980407-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012177.5(FBXO5):c.103+2450A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 151,912 control chromosomes in the GnomAD database, including 961 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 0.11 (961 hom., cov: 32)
• Consequence: FBXO5 NM_012177.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

Genes affected

FBXO5 (HGNC:13584): (F-box protein 5) 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. This protein is similar to xenopus early mitotic inhibitor-1 (Emi1), which is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO5	NM_012177.5	c.103+2450A>G		intron_variant		ENST00000229758.8
FBXO5	NM_001142522.3	c.-36+2827A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO5	ENST00000229758.8	c.103+2450A>G		intron_variant		1	NM_012177.5	P4
FBXO5	ENST00000367241.3	c.-36+2827A>G		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16504 AN: 151794 Hom.: 961 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.0819

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

GnomAD4 genome AF: 0.109 AC: 16505 AN: 151912 Hom.: 961 Cov.: 32 AF XY: 0.111 AC XY: 8248 AN XY: 74268

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0626

Gnomad4 ASJ AF: 0.0450

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0979

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0944 Hom.: 1481

Bravo AF: 0.101

Asia WGS AF: 0.157 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.4
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9479476; hg19: chr6-153301542;