dbSNP rs1712: FBXO5:c.*433G>A (chr6-152970730-C-T) – 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.*433G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,700 control chromosomes in the GnomAD database, including 3,496 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 0.21 ( 3488 hom., cov: 32)

Exomes 𝑓: 0.12 ( 8 hom. )

Consequence

FBXO5
NM_012177.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.638

Publications

16 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:

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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=-0.69).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012177.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO5	NM_012177.5	MANE Select	c.*433G>A		3_prime_UTR	Exon 5 of 5	NP_036309.1
	FBXO5	NM_001142522.3		c.*433G>A		3_prime_UTR	Exon 5 of 5	NP_001135994.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FBXO5	ENST00000229758.8	TSL:1 MANE Select	c.*433G>A	3_prime_UTR	Exon 5 of 5	ENSP00000229758.3
FBXO5	ENST00000367241.3	TSL:1	c.*433G>A	3_prime_UTR	Exon 5 of 5	ENSP00000356210.3
FBXO5	ENST00000477822.2	TSL:2	n.2399G>A	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31341

AN:

151852

Hom.:

3477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.0914

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.0732

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.170

GnomAD4 exome

AF:

0.124

AC:

AN:

732

Hom.:

Cov.:

AF XY:

0.148

AC XY:

AN XY:

378

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.179

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.192

AC:

AN:

European-Finnish (FIN)

AF:

0.154

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.106

AC:

AN:

546

Other (OTH)

AF:

0.133

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.207

AC:

31397

AN:

151968

Hom.:

3488

Cov.:

AF XY:

0.208

AC XY:

15492

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.288

AC:

11932

AN:

41438

American (AMR)

AF:

0.242

AC:

3695

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0914

AC:

317

AN:

3470

East Asian (EAS)

AF:

0.134

AC:

695

AN:

5168

South Asian (SAS)

AF:

0.269

AC:

1294

AN:

4814

European-Finnish (FIN)

AF:

0.174

AC:

1834

AN:

10568

Middle Eastern (MID)

AF:

0.0753

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.163

AC:

11084

AN:

67932

Other (OTH)

AF:

0.171

AC:

361

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1259

2518

3776

5035

6294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.200

Hom.:

997

Bravo

AF:

0.213

Asia WGS

AF:

0.212

AC:

733

AN:

3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

8.5

(source)

DANN

Benign

0.62

PhyloP100

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over