22-32474782-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000886522.1(FBXO7):​c.-221C>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 0.431 in 535,918 control chromosomes in the GnomAD database, including 53,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17762 hom., cov: 32)
  • Exomes 𝑓: 0.42 (35273 hom.)
• Consequence: FBXO7 ENST00000886522.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 22-32474782-C-T is Benign according to our data. Variant chr22-32474782-C-T is described in ClinVar as Benign. ClinVar VariationId is 341299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

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>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.-221C>T		5_prime_UTR	Exon 1 of 8	ENSP00000556581.1
	FBXO7	ENST00000886523.1		c.-221C>T		5_prime_UTR	Exon 1 of 8	ENSP00000556582.1
	FBXO7	ENST00000420700.5	TSL:5	n.-221C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000406155.1	F8WBR0

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71085 AN: 151816 Hom.: 17724 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.416 AC: 159742 AN: 383984 Hom.: 35273 Cov.: 4 AF XY: 0.420 AC XY: 84776 AN XY: 201770

African (AFR) AF: 0.633 AC: 4780 AN: 7556

American (AMR) AF: 0.502 AC: 5855 AN: 11664

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 4353 AN: 11438

East Asian (EAS) AF: 0.654 AC: 15672 AN: 23962

South Asian (SAS) AF: 0.509 AC: 18894 AN: 37106

European-Finnish (FIN) AF: 0.444 AC: 12088 AN: 27212

Middle Eastern (MID) AF: 0.403 AC: 704 AN: 1746

European-Non Finnish (NFE) AF: 0.365 AC: 87738 AN: 240684

Other (OTH) AF: 0.427 AC: 9658 AN: 22616

GnomAD4 genome AF: 0.468 AC: 71174 AN: 151934 Hom.: 17762 Cov.: 32 AF XY: 0.475 AC XY: 35249 AN XY: 74254

African (AFR) AF: 0.628 AC: 26066 AN: 41476

American (AMR) AF: 0.459 AC: 7011 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1350 AN: 3472

East Asian (EAS) AF: 0.613 AC: 3123 AN: 5092

South Asian (SAS) AF: 0.495 AC: 2385 AN: 4816

European-Finnish (FIN) AF: 0.485 AC: 5132 AN: 10574

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24776 AN: 67900

Other (OTH) AF: 0.429 AC: 906 AN: 2114

Alfa AF: 0.406 Hom.: 1600

Bravo AF: 0.474

Asia WGS AF: 0.598 AC: 2077 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Parkinson Disease, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.5
DANN	Benign	0.95
PhyloP100		-0.92
PromoterAI		0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

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;