Genetic Variant FBXO7:c.-268C>A (chr22-32474735-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000886522.1(FBXO7):c.-268C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000334 in 299,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

FBXO7
ENST00000886522.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.58

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

parkinsonian-pyramidal syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

FBXO7 links:

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new If you want to explore the variant's impact on the transcript ENST00000886522.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000886522.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO7	NM_012179.4	MANE Select	c.-268C>A		upstream_gene	N/A	NP_036311.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FBXO7	ENST00000886522.1		c.-268C>A	5_prime_UTR	Exon 1 of 8	ENSP00000556581.1
FBXO7	ENST00000886523.1		c.-268C>A	5_prime_UTR	Exon 1 of 8	ENSP00000556582.1
FBXO7	ENST00000420700.5	TSL:5	n.-268C>A	non_coding_transcript_exon	Exon 1 of 8	ENSP00000406155.1	F8WBR0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000333

AC:

AN:

299850

Hom.:

Cov.:

AF XY:

0.00000637

AC XY:

AN XY:

156978

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6362

American (AMR)

AF:

0.00

AC:

AN:

7614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9700

East Asian (EAS)

AF:

0.00

AC:

AN:

19302

South Asian (SAS)

AF:

0.0000379

AC:

AN:

26420

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1416

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

188256

Other (OTH)

AF:

0.00

AC:

AN:

18324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0080

(source)

DANN

Benign

0.44

PhyloP100

-3.6

PromoterAI

-0.073

Neutral

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over