rs8140067

Variant names:

• chr22-32475455-C-A
• rs8140067
• NM_012179.4:c.122+331C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-32475455-C-A
• chr22-32475455-C-G
• chr22-32475455-C-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.122+331C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,595,388 control chromosomes in the GnomAD database, including 33,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2736 hom., cov: 33)
  • Exomes 𝑓: 0.20 (30595 hom.)
• Consequence: FBXO7 NM_012179.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.19
• Publications: 10 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), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 22-32475455-C-A is Benign according to our data. Variant chr22-32475455-C-A is described in ClinVar as Benign. ClinVar VariationId is 1230871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO7	NM_012179.4	c.122+331C>A		intron_variant	Intron 1 of 8	ENST00000266087.12	NP_036311.3
FBXO7	NM_001033024.2	c.37+57C>A		intron_variant	Intron 1 of 8		NP_001028196.1
FBXO7	NM_001257990.2	c.-221+57C>A		intron_variant	Intron 1 of 8		NP_001244919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO7	ENST00000266087.12	c.122+331C>A		intron_variant	Intron 1 of 8	1	NM_012179.4	ENSP00000266087.7

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28692 AN: 152068 Hom.: 2732 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.204 AC: 294038 AN: 1443202 Hom.: 30595 Cov.: 28 AF XY: 0.202 AC XY: 145226 AN XY: 717832

African (AFR) AF: 0.140 AC: 4455 AN: 31760

American (AMR) AF: 0.199 AC: 8610 AN: 43362

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 6520 AN: 25698

East Asian (EAS) AF: 0.187 AC: 7157 AN: 38226

South Asian (SAS) AF: 0.132 AC: 11139 AN: 84300

European-Finnish (FIN) AF: 0.219 AC: 11488 AN: 52490

Middle Eastern (MID) AF: 0.243 AC: 1390 AN: 5726

European-Non Finnish (NFE) AF: 0.210 AC: 231423 AN: 1101958

Other (OTH) AF: 0.199 AC: 11856 AN: 59682

GnomAD4 genome AF: 0.189 AC: 28711 AN: 152186 Hom.: 2736 Cov.: 33 AF XY: 0.189 AC XY: 14072 AN XY: 74384

African (AFR) AF: 0.145 AC: 6031 AN: 41550

American (AMR) AF: 0.205 AC: 3129 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3470

East Asian (EAS) AF: 0.155 AC: 799 AN: 5162

South Asian (SAS) AF: 0.126 AC: 609 AN: 4822

European-Finnish (FIN) AF: 0.236 AC: 2500 AN: 10572

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14185 AN: 67998

Other (OTH) AF: 0.184 AC: 388 AN: 2110

Alfa AF: 0.195 Hom.: 9316

Bravo AF: 0.185

Asia WGS AF: 0.128 AC: 444 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.029
DANN	Benign	0.44
PhyloP100		-3.2
PromoterAI		-0.017	Neutral
Mutation Taster		=100/0	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: rs8140067; hg19: chr22-32871442; COSMIC: COSV56681347; COSMIC: COSV56681347;