rs330787

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001190274.2(FBXO11):​c.2007-371T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 186,678 control chromosomes in the GnomAD database, including 43,090 homozygotes. 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 0.69 ( 36396 hom., cov: 30)
Exomes 𝑓: 0.61 ( 6694 hom. )

Consequence

FBXO11
NM_001190274.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00400
Variant links:
Genes affected
FBXO11 (HGNC:13590): (F-box protein 11) 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 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. It can function as an arginine methyltransferase that symmetrically dimethylates arginine residues, and it acts as an adaptor protein to mediate the neddylation of p53, which leads to the suppression of p53 function. This gene is known to be down-regulated in melanocytes from patients with vitiligo, a skin disorder that results in depigmentation. Polymorphisms in this gene are associated with chronic otitis media with effusion and recurrent otitis media (COME/ROM), a hearing loss disorder, and the knockout of the homologous mouse gene results in the deaf mouse mutant Jeff (Jf), a single gene model of otitis media. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FBXO11NM_001190274.2 linkuse as main transcriptc.2007-371T>C intron_variant ENST00000403359.8 NP_001177203.1 Q86XK2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FBXO11ENST00000403359.8 linkuse as main transcriptc.2007-371T>C intron_variant 1 NM_001190274.2 ENSP00000384823.4 Q86XK2-1

Frequencies

GnomAD3 genomes
AF:
0.686
AC:
104096
AN:
151816
Hom.:
36324
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.833
Gnomad AMI
AF:
0.618
Gnomad AMR
AF:
0.639
Gnomad ASJ
AF:
0.652
Gnomad EAS
AF:
0.470
Gnomad SAS
AF:
0.595
Gnomad FIN
AF:
0.652
Gnomad MID
AF:
0.706
Gnomad NFE
AF:
0.637
Gnomad OTH
AF:
0.681
GnomAD4 exome
AF:
0.610
AC:
21209
AN:
34744
Hom.:
6694
Cov.:
0
AF XY:
0.609
AC XY:
11267
AN XY:
18506
show subpopulations
Gnomad4 AFR exome
AF:
0.813
Gnomad4 AMR exome
AF:
0.604
Gnomad4 ASJ exome
AF:
0.615
Gnomad4 EAS exome
AF:
0.442
Gnomad4 SAS exome
AF:
0.617
Gnomad4 FIN exome
AF:
0.617
Gnomad4 NFE exome
AF:
0.616
Gnomad4 OTH exome
AF:
0.637
GnomAD4 genome
AF:
0.686
AC:
104229
AN:
151934
Hom.:
36396
Cov.:
30
AF XY:
0.684
AC XY:
50754
AN XY:
74234
show subpopulations
Gnomad4 AFR
AF:
0.834
Gnomad4 AMR
AF:
0.640
Gnomad4 ASJ
AF:
0.652
Gnomad4 EAS
AF:
0.469
Gnomad4 SAS
AF:
0.597
Gnomad4 FIN
AF:
0.652
Gnomad4 NFE
AF:
0.637
Gnomad4 OTH
AF:
0.684
Alfa
AF:
0.640
Hom.:
41564
Bravo
AF:
0.689
Asia WGS
AF:
0.571
AC:
1986
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
0.94
DANN
Benign
0.36

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs330787; hg19: chr2-48041377; API