ENST00000886522.1:c.-221C>A

Variant names:

• chr22-32474782-C-A
• rs2072814
• ENST00000886522.1:c.-221C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000886522.1(FBXO7):​c.-221C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FBXO7 ENST00000886522.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915
• Publications: 7 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: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).

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.-221C>A		upstream_gene	N/A	NP_036311.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO7	ENST00000886522.1		c.-221C>A		5_prime_UTR	Exon 1 of 8	ENSP00000556581.1
	FBXO7	ENST00000886523.1		c.-221C>A		5_prime_UTR	Exon 1 of 8	ENSP00000556582.1
	FBXO7	ENST00000420700.5	TSL:5	n.-221C>A		non_coding_transcript_exon	Exon 1 of 8	ENSP00000406155.1	F8WBR0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 384624 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 202108

African (AFR) AF: 0.00 AC: 0 AN: 7572

American (AMR) AF: 0.00 AC: 0 AN: 11680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11460

East Asian (EAS) AF: 0.00 AC: 0 AN: 24002

South Asian (SAS) AF: 0.00 AC: 0 AN: 37118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 241090

Other (OTH) AF: 0.00 AC: 0 AN: 22664

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1600

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.2
DANN	Benign	0.87
PhyloP100		-0.92
PromoterAI		0.096	Neutral

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

Other links and lift over

dbSNP: rs2072814; hg19: chr22-32870769;