2-47867198-G-C

Variant names:

• chr2-47867198-G-C
• rs874869
• NM_001190274.2:c.233-27429C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001190274.2(FBXO11):​c.233-27429C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,936 control chromosomes in the GnomAD database, including 23,279 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 0.55 (23279 hom., cov: 31)
• Consequence: FBXO11 NM_001190274.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 6 publications found

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]

FBXO11 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with dysmorphic facies and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO11	NM_001190274.2	c.233-27429C>G		intron_variant	Intron 1 of 22	ENST00000403359.8	NP_001177203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO11	ENST00000403359.8	c.233-27429C>G		intron_variant	Intron 1 of 22	1	NM_001190274.2	ENSP00000384823.4

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83884 AN: 151818 Hom.: 23243 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.523

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.553 AC: 83975 AN: 151936 Hom.: 23279 Cov.: 31 AF XY: 0.550 AC XY: 40886 AN XY: 74280

African (AFR) AF: 0.585 AC: 24235 AN: 41426

American (AMR) AF: 0.549 AC: 8372 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2045 AN: 3470

East Asian (EAS) AF: 0.628 AC: 3245 AN: 5170

South Asian (SAS) AF: 0.514 AC: 2473 AN: 4814

European-Finnish (FIN) AF: 0.511 AC: 5373 AN: 10524

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.537 AC: 36511 AN: 67962

Other (OTH) AF: 0.524 AC: 1104 AN: 2108

Alfa AF: 0.426 Hom.: 1178

Bravo AF: 0.558

Asia WGS AF: 0.595 AC: 2071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.42
PhyloP100		-1.2
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: rs874869; hg19: chr2-48094337;