rs11107

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012179.4(FBXO7):c.345G>A(p.Met115Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,613,402 control chromosomes in the GnomAD database, including 136,759 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13649 hom., cov: 30)

Exomes 𝑓: 0.40 ( 123110 hom. )

Consequence

FBXO7
NM_012179.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0270

Variant links:

Genes affected

FBXO7 (HGNC:13586): (F-box protein 7) 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 and it may play a role in regulation of hematopoiesis. Alternatively spliced transcript variants of this gene have been identified with the full-length natures of only some variants being determined. [provided by RefSeq, Jul 2008]

FBXO7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.0905507E-6).

BP6

Variant 22-32479203-G-A is Benign according to our data. Variant chr22-32479203-G-A is described in ClinVar as [Benign]. Clinvar id is 195275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-32479203-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FBXO7	NM_012179.4 linkuse as main transcript	c.345G>A	p.Met115Ile	missense_variant	2/9	ENST00000266087.12	NP_036311.3
FBXO7	NM_001257990.2 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	2/9		NP_001244919.1
FBXO7	NM_001033024.2 linkuse as main transcript	c.108G>A	p.Met36Ile	missense_variant	2/9		NP_001028196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO7	ENST00000266087.12 linkuse as main transcript	c.345G>A	p.Met115Ile	missense_variant	2/9	1	NM_012179.4	ENSP00000266087	P2	Q9Y3I1-1

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63089

AN:

151522

Hom.:

13628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.687

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.496

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.398

GnomAD3 exomes

AF:

0.453

AC:

113761

AN:

251364

Hom.:

27224

AF XY:

0.447

AC XY:

60780

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.388

Gnomad AMR exome

AF:

0.606

Gnomad ASJ exome

AF:

0.409

Gnomad EAS exome

AF:

0.687

Gnomad SAS exome

AF:

0.474

Gnomad FIN exome

AF:

0.481

Gnomad NFE exome

AF:

0.371

Gnomad OTH exome

AF:

0.429

GnomAD4 exome

AF:

0.402

AC:

588283

AN:

1461758

Hom.:

123110

Cov.:

AF XY:

0.405

AC XY:

294181

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.380

Gnomad4 AMR exome

AF:

0.595

Gnomad4 ASJ exome

AF:

0.406

Gnomad4 EAS exome

AF:

0.736

Gnomad4 SAS exome

AF:

0.466

Gnomad4 FIN exome

AF:

0.469

Gnomad4 NFE exome

AF:

0.374

Gnomad4 OTH exome

AF:

0.416

GnomAD4 genome

AF:

0.416

AC:

63145

AN:

151644

Hom.:

13649

Cov.:

AF XY:

0.425

AC XY:

31503

AN XY:

74086

show subpopulations

Gnomad4 AFR

AF:

0.387

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.418

Gnomad4 EAS

AF:

0.687

Gnomad4 SAS

AF:

0.459

Gnomad4 FIN

AF:

0.496

Gnomad4 NFE

AF:

0.380

Gnomad4 OTH

AF:

0.401

Alfa

AF:

0.392

Hom.:

29586

Bravo

AF:

0.418

TwinsUK

AF:

0.361

AC:

1340

ALSPAC

AF:

0.373

AC:

1437

ESP6500AA

AF:

0.372

AC:

1640

ESP6500EA

AF:

0.372

AC:

3202

ExAC

AF:

0.440

AC:

53403

Asia WGS

AF:

0.594

AC:

2063

AN:

3478

EpiCase

AF:

0.374

EpiControl

AF:

0.375

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Parkinsonian-pyramidal syndrome

Benign:5

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	Apr 22, 2016	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	This variant is associated with the following publications: (PMID: 23222517) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 21, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

2.6

DANN

Benign

0.39

DEOGEN2

Benign

0.033

T;.;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.082

T;T;D;D

MetaRNN

Benign

0.0000021

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-2.0

N;.;.;.

MutationTaster

Benign

5.5e-25

P;P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.17

N;N;N;N

REVEL

Benign

0.089

Sift

Benign

0.22

T;T;T;T

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.010

MutPred

0.053

Gain of glycosylation at S114 (P = 0.0537);.;.;.;

MPC

0.070

ClinPred

0.0057

GERP RS

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.078

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over