Genetic Variant NM_012177.5: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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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