rs4381823

Variant summary

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

The NM_001190274.2(FBXO11):​c.1797+166T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 152,266 control chromosomes in the GnomAD database, including 249 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 0.056 ( 249 hom., cov: 32)

Consequence

FBXO11
NM_001190274.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.553
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=-0.83).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FBXO11NM_001190274.2 linkuse as main transcriptc.1797+166T>C intron_variant ENST00000403359.8 NP_001177203.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FBXO11ENST00000403359.8 linkuse as main transcriptc.1797+166T>C intron_variant 1 NM_001190274.2 ENSP00000384823 Q86XK2-1

Frequencies

GnomAD3 genomes
AF:
0.0557
AC:
8468
AN:
152148
Hom.:
247
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0519
Gnomad AMI
AF:
0.0504
Gnomad AMR
AF:
0.0335
Gnomad ASJ
AF:
0.0784
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.0428
Gnomad FIN
AF:
0.0437
Gnomad MID
AF:
0.0475
Gnomad NFE
AF:
0.0690
Gnomad OTH
AF:
0.0511
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0557
AC:
8474
AN:
152266
Hom.:
249
Cov.:
32
AF XY:
0.0527
AC XY:
3925
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0519
Gnomad4 AMR
AF:
0.0334
Gnomad4 ASJ
AF:
0.0784
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.0435
Gnomad4 FIN
AF:
0.0437
Gnomad4 NFE
AF:
0.0690
Gnomad4 OTH
AF:
0.0506
Alfa
AF:
0.0640
Hom.:
53
Bravo
AF:
0.0538
Asia WGS
AF:
0.0200
AC:
69
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
6.2
DANN
Benign
0.42

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: rs4381823; hg19: chr2-48047335; API