dbSNP rs9479476: FBXO5:c.103+2450A>G (chr6-152980407-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0370

Publications

4 publications found

Variant links:

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]

FBXO5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FBXO5	NM_012177.5 link	c.103+2450A>G		intron_variant	Intron 1 of 4	ENST00000229758.8	NP_036309.1	Q9UKT4-1
FBXO5	NM_001142522.3 link	c.-36+2827A>G		intron_variant	Intron 1 of 4		NP_001135994.1	Q9UKT4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO5	ENST00000229758.8 link	c.103+2450A>G		intron_variant	Intron 1 of 4	1	NM_012177.5	ENSP00000229758.3		Q9UKT4-1
FBXO5	ENST00000367241.3 link	c.-36+2827A>G		intron_variant	Intron 1 of 4	1		ENSP00000356210.3		Q9UKT4-2

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16504

AN:

151794

Hom.:

961

Cov.:

show subpopulations

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.:

AF XY:

0.111

AC XY:

8248

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.138

AC:

5692

AN:

41384

American (AMR)

AF:

0.0626

AC:

955

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0450

AC:

156

AN:

3466

East Asian (EAS)

AF:

0.111

AC:

573

AN:

5166

South Asian (SAS)

AF:

0.200

AC:

963

AN:

4822

European-Finnish (FIN)

AF:

0.118

AC:

1247

AN:

10552

Middle Eastern (MID)

AF:

0.0377

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0979

AC:

6652

AN:

67950

Other (OTH)

AF:

0.0810

AC:

171

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

767

1534

2300

3067

3834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0983

Hom.:

3313

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

(source)

DANN

Benign

0.71

PhyloP100

-0.037

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over