Variant 22-32474819-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012179.4(FBXO7):c.-184C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 622,726 control chromosomes in the GnomAD database, including 11,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2192 hom., cov: 33)

Exomes 𝑓: 0.18 ( 9454 hom. )

Consequence

FBXO7
NM_012179.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.165

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 (BayesDel_noAF=-0.74).

BP6

Variant 22-32474819-C-T is Benign according to our data. Variant chr22-32474819-C-T is described in ClinVar as [Benign]. Clinvar id is 341302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO7	NM_012179.4 linkuse as main transcript	c.-184C>T		5_prime_UTR_variant	1/9	ENST00000266087.12	NP_036311.3	Q9Y3I1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO7	ENST00000266087 linkuse as main transcript	c.-184C>T		5_prime_UTR_variant	1/9	1	NM_012179.4	ENSP00000266087.7		Q9Y3I1-1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22401

AN:

152042

Hom.:

2192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0411

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0506

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.149

GnomAD4 exome

AF:

0.184

AC:

86469

AN:

470566

Hom.:

9454

Cov.:

AF XY:

0.178

AC XY:

43790

AN XY:

246262

show subpopulations

Gnomad4 AFR exome

AF:

0.0342

Gnomad4 AMR exome

AF:

0.103

Gnomad4 ASJ exome

AF:

0.168

Gnomad4 EAS exome

AF:

0.000146

Gnomad4 SAS exome

AF:

0.0627

Gnomad4 FIN exome

AF:

0.180

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.147

AC:

22404

AN:

152160

Hom.:

2192

Cov.:

AF XY:

0.140

AC XY:

10413

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0409

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.0506

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.231

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.205

Hom.:

656

Bravo

AF:

0.142

Asia WGS

AF:

0.0330

AC:

114

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Parkinsonian-pyramidal syndrome

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.2

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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