22-32491163-C-T

Position:

chr22-32491163-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_012179.4(FBXO7):c.949C>T(p.Leu317=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,606,990 control chromosomes in the GnomAD database, including 136,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13664 hom., cov: 31)

Exomes 𝑓: 0.40 ( 122668 hom. )

Consequence

FBXO7
NM_012179.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.36

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 22-32491163-C-T is Benign according to our data. Variant chr22-32491163-C-T is described in ClinVar as [Benign]. Clinvar id is 341314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-32491163-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FBXO7	NM_012179.4 linkuse as main transcript	c.949C>T	p.Leu317=	synonymous_variant	6/9	ENST00000266087.12
FBXO7	NM_001033024.2 linkuse as main transcript	c.712C>T	p.Leu238=	synonymous_variant	6/9
FBXO7	NM_001257990.2 linkuse as main transcript	c.607C>T	p.Leu203=	synonymous_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO7	ENST00000266087.12 linkuse as main transcript	c.949C>T	p.Leu317=	synonymous_variant	6/9	1	NM_012179.4	P2	Q9Y3I1-1

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63190

AN:

151768

Hom.:

13645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.689

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.496

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.397

GnomAD3 exomes

AF:

0.453

AC:

113653

AN:

251146

Hom.:

27194

AF XY:

0.447

AC XY:

60736

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.606

Gnomad ASJ exome

AF:

0.408

Gnomad EAS exome

AF:

0.687

Gnomad SAS exome

AF:

0.475

Gnomad FIN exome

AF:

0.481

Gnomad NFE exome

AF:

0.371

Gnomad OTH exome

AF:

0.430

GnomAD4 exome

AF:

0.402

AC:

584951

AN:

1455106

Hom.:

122668

Cov.:

AF XY:

0.404

AC XY:

292696

AN XY:

724178

show subpopulations

Gnomad4 AFR exome

AF:

0.379

Gnomad4 AMR exome

AF:

0.595

Gnomad4 ASJ exome

AF:

0.406

Gnomad4 EAS exome

AF:

0.736

Gnomad4 SAS exome

AF:

0.467

Gnomad4 FIN exome

AF:

0.469

Gnomad4 NFE exome

AF:

0.374

Gnomad4 OTH exome

AF:

0.416

GnomAD4 genome

AF:

0.416

AC:

63241

AN:

151884

Hom.:

13664

Cov.:

AF XY:

0.426

AC XY:

31578

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.387

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.418

Gnomad4 EAS

AF:

0.689

Gnomad4 SAS

AF:

0.460

Gnomad4 FIN

AF:

0.496

Gnomad4 NFE

AF:

0.380

Gnomad4 OTH

AF:

0.400

Alfa

AF:

0.390

Hom.:

11155

Bravo

AF:

0.418

Asia WGS

AF:

0.594

AC:

2063

AN:

3478

EpiCase

AF:

0.375

EpiControl

AF:

0.375

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Parkinsonian-pyramidal syndrome

Benign:5

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	Mar 28, 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 13, 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	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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