22-32474819-C-T

Variant names:

• chr22-32474819-C-T
• rs11538371
• NM_012179.4:c.-184C>T

Variant summary

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

The NM_012179.4(FBXO7):​c.-184C>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 0.175 in 622,726 control chromosomes in the GnomAD database, including 11,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2192 hom., cov: 33)
  • Exomes 𝑓: 0.18 (9454 hom.)
• Consequence: FBXO7 NM_012179.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.165
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 22-32474819-C-T is Benign according to our data. Variant chr22-32474819-C-T is described in ClinVar as Benign. ClinVar VariationId is 341302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 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.-184C>T		5_prime_UTR	Exon 1 of 9	NP_036311.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO7	ENST00000266087.12	TSL:1 MANE Select	c.-184C>T		5_prime_UTR	Exon 1 of 9	ENSP00000266087.7	Q9Y3I1-1
	FBXO7	ENST00000920428.1		c.-184C>T		5_prime_UTR	Exon 1 of 9	ENSP00000590487.1
	FBXO7	ENST00000886522.1		c.-184C>T		5_prime_UTR	Exon 1 of 8	ENSP00000556581.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22401 AN: 152042 Hom.: 2192 Cov.: 33

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0506

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.184 AC: 86469 AN: 470566 Hom.: 9454 Cov.: 6 AF XY: 0.178 AC XY: 43790 AN XY: 246262

African (AFR) AF: 0.0342 AC: 325 AN: 9490

American (AMR) AF: 0.103 AC: 1628 AN: 15824

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 2141 AN: 12708

East Asian (EAS) AF: 0.000146 AC: 4 AN: 27382

South Asian (SAS) AF: 0.0627 AC: 2743 AN: 43730

European-Finnish (FIN) AF: 0.180 AC: 5225 AN: 28962

Middle Eastern (MID) AF: 0.0787 AC: 157 AN: 1996

European-Non Finnish (NFE) AF: 0.229 AC: 69761 AN: 304244

Other (OTH) AF: 0.171 AC: 4485 AN: 26230

GnomAD4 genome AF: 0.147 AC: 22404 AN: 152160 Hom.: 2192 Cov.: 33 AF XY: 0.140 AC XY: 10413 AN XY: 74402

African (AFR) AF: 0.0409 AC: 1701 AN: 41546

American (AMR) AF: 0.124 AC: 1894 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3472

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5164

South Asian (SAS) AF: 0.0506 AC: 244 AN: 4822

European-Finnish (FIN) AF: 0.161 AC: 1703 AN: 10604

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15712 AN: 67934

Other (OTH) AF: 0.149 AC: 315 AN: 2112

Alfa AF: 0.201 Hom.: 656

Bravo AF: 0.142

Asia WGS AF: 0.0330 AC: 114 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Parkinsonian-pyramidal syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.2
DANN	Benign	0.80
PhyloP100		-0.17
PromoterAI		0.0057	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: rs11538371; hg19: chr22-32870806;