rs41311141

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_012179.4(FBXO7):c.540A>G(p.Pro180Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 1,614,148 control chromosomes in the GnomAD database, including 1,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 127 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1498 hom. )

Consequence

FBXO7
NM_012179.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.93

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:

FBXO7 (HGNC:):

FBXO7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 22-32484019-A-G is Benign according to our data. Variant chr22-32484019-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 341311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-32484019-A-G is described in Lovd as [Likely_benign]. Variant chr22-32484019-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.93 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0319 (4857/152316) while in subpopulation NFE AF= 0.0461 (3138/68024). AF 95% confidence interval is 0.0448. There are 127 homozygotes in gnomad4. There are 2414 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 127 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO7	NM_012179.4 linkuse as main transcript	c.540A>G	p.Pro180Pro	synonymous_variant	3/9	ENST00000266087.12	NP_036311.3	Q9Y3I1-1
FBXO7	NM_001033024.2 linkuse as main transcript	c.303A>G	p.Pro101Pro	synonymous_variant	3/9		NP_001028196.1	Q9Y3I1-2
FBXO7	NM_001257990.2 linkuse as main transcript	c.198A>G	p.Pro66Pro	synonymous_variant	3/9		NP_001244919.1	Q9Y3I1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO7	ENST00000266087.12 linkuse as main transcript	c.540A>G	p.Pro180Pro	synonymous_variant	3/9	1	NM_012179.4	ENSP00000266087.7		Q9Y3I1-1

Frequencies

GnomAD3 genomes

AF:

0.0319

AC:

4858

AN:

152198

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00774

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0208

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.0838

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0461

Gnomad OTH

AF:

0.0277

GnomAD3 exomes

AF:

0.0338

AC:

8497

AN:

251440

Hom.:

211

AF XY:

0.0335

AC XY:

4556

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00744

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00980

Gnomad FIN exome

AF:

0.0877

Gnomad NFE exome

AF:

0.0462

Gnomad OTH exome

AF:

0.0354

GnomAD4 exome

AF:

0.0416

AC:

60827

AN:

1461832

Hom.:

1498

Cov.:

AF XY:

0.0409

AC XY:

29712

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00574

Gnomad4 AMR exome

AF:

0.0161

Gnomad4 ASJ exome

AF:

0.0215

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00992

Gnomad4 FIN exome

AF:

0.0849

Gnomad4 NFE exome

AF:

0.0466

Gnomad4 OTH exome

AF:

0.0349

GnomAD4 genome

AF:

0.0319

AC:

4857

AN:

152316

Hom.:

127

Cov.:

AF XY:

0.0324

AC XY:

2414

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00772

Gnomad4 AMR

AF:

0.0208

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.0838

Gnomad4 NFE

AF:

0.0461

Gnomad4 OTH

AF:

0.0274

Alfa

AF:

0.0224

Hom.:

Bravo

AF:

0.0266

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0427

EpiControl

AF:

0.0423

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Parkinsonian-pyramidal syndrome

Benign:4

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	Jul 21, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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	clinical testing	GeneDx	Sep 21, 2018	This variant is associated with the following publications: (PMID: 27861377) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.8

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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