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:

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=-0.69).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO5	NM_012177.5 link	c.*433G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000229758.8	NP_036309.1	Q9UKT4-1
FBXO5	NM_001142522.3 link	c.*433G>A		3_prime_UTR_variant	Exon 5 of 5		NP_001135994.1	Q9UKT4-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBXO5	ENST00000229758.8 link	c.*433G>A	3_prime_UTR_variant	Exon 5 of 5	1	NM_012177.5	ENSP00000229758.3	Q9UKT4-1
FBXO5	ENST00000367241.3 link	c.*433G>A	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000356210.3	Q9UKT4-2
FBXO5	ENST00000477822.2 link	n.2399G>A	non_coding_transcript_exon_variant	Exon 2 of 2	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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over