22-32474735-C-T

Variant names:

• chr22-32474735-C-T
• rs540551581
• ENST00000886522.1:c.-268C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The ENST00000886522.1(FBXO7):​c.-268C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000619 in 452,078 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: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000083 (0 hom.)
• Consequence: FBXO7 ENST00000886522.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.58
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000834 (25/299848) while in subpopulation SAS AF = 0.000833 (22/26418). AF 95% confidence interval is 0.000563. There are 0 homozygotes in GnomAdExome4. There are 21 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

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>T		upstream_gene	N/A	NP_036311.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO7	ENST00000886522.1		c.-268C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000556581.1
	FBXO7	ENST00000886523.1		c.-268C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000556582.1
	FBXO7	ENST00000886522.1		c.-268C>T		5_prime_UTR	Exon 1 of 8	ENSP00000556581.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000834 AC: 25 AN: 299848 Hom.: 0 Cov.: 0 AF XY: 0.000134 AC XY: 21 AN XY: 156976

African (AFR) AF: 0.00 AC: 0 AN: 6362

American (AMR) AF: 0.00 AC: 0 AN: 7614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9700

East Asian (EAS) AF: 0.00 AC: 0 AN: 19302

South Asian (SAS) AF: 0.000833 AC: 22 AN: 26418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1416

European-Non Finnish (NFE) AF: 0.00000531 AC: 1 AN: 188256

Other (OTH) AF: 0.000109 AC: 2 AN: 18324

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152230 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74376

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000620 AC: 3 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.012
DANN	Benign	0.84
PhyloP100		-3.6
PromoterAI		0.14	Neutral
Mutation Taster		=300/0	polymorphism

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: rs540551581; hg19: chr22-32870722;