22-32484598-T-C

Variant names:

• chr22-32484598-T-C
• rs5749446
• NM_012179.4:c.646-470T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012179.4(FBXO7):​c.646-470T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,896 control chromosomes in the GnomAD database, including 13,703 homozygotes. 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: 𝑓 0.42 (13703 hom., cov: 32)
• Consequence: FBXO7 NM_012179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 26 publications found

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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012179.4. 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.646-470T>C		intron	N/A	NP_036311.3
	FBXO7	NM_001033024.2		c.409-470T>C		intron	N/A	NP_001028196.1	Q9Y3I1-2
	FBXO7	NM_001257990.2		c.304-470T>C		intron	N/A	NP_001244919.1	Q9Y3I1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO7	ENST00000266087.12	TSL:1 MANE Select	c.646-470T>C		intron	N/A	ENSP00000266087.7	Q9Y3I1-1
	FBXO7	ENST00000886524.1		c.646-470T>C		intron	N/A	ENSP00000556583.1
	FBXO7	ENST00000920428.1		c.646-470T>C		intron	N/A	ENSP00000590487.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63280 AN: 151778 Hom.: 13684 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.417 AC: 63332 AN: 151896 Hom.: 13703 Cov.: 32 AF XY: 0.426 AC XY: 31601 AN XY: 74228

African (AFR) AF: 0.388 AC: 16055 AN: 41400

American (AMR) AF: 0.506 AC: 7720 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1452 AN: 3468

East Asian (EAS) AF: 0.690 AC: 3552 AN: 5150

South Asian (SAS) AF: 0.461 AC: 2225 AN: 4824

European-Finnish (FIN) AF: 0.497 AC: 5242 AN: 10544

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25796 AN: 67934

Other (OTH) AF: 0.400 AC: 845 AN: 2110

Alfa AF: 0.397 Hom.: 20827

Bravo AF: 0.419

Asia WGS AF: 0.595 AC: 2066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.64
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5749446; hg19: chr22-32880585;