2-47853121-C-G

Variant names:

• chr2-47853121-C-G
• rs2937345
• NM_001190274.2:c.233-13352G>C

Variant summary

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

The NM_001190274.2(FBXO11):​c.233-13352G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,508 control chromosomes in the GnomAD database, including 35,160 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 0.67 (35160 hom., cov: 27)
• Consequence: FBXO11 NM_001190274.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 2 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190274.2. 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
	FBXO11	NM_001190274.2	MANE Select	c.233-13352G>C		intron	N/A	NP_001177203.1	Q86XK2-1
	FBXO11	NM_001374325.1		c.-20-13352G>C		intron	N/A	NP_001361254.1	Q86XK2-6
	FBXO11	NM_025133.4		c.-20-13352G>C		intron	N/A	NP_079409.3	Q86XK2-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO11	ENST00000403359.8	TSL:1 MANE Select	c.233-13352G>C		intron	N/A	ENSP00000384823.4	Q86XK2-1
	FBXO11	ENST00000402508.5	TSL:1	c.-20-13352G>C		intron	N/A	ENSP00000385398.1	Q86XK2-6
	FBXO11	ENST00000492225.5	TSL:1	n.81-13352G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.673 AC: 101903 AN: 151390 Hom.: 35094 Cov.: 27

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.673 AC: 102028 AN: 151508 Hom.: 35160 Cov.: 27 AF XY: 0.668 AC XY: 49487 AN XY: 74028

African (AFR) AF: 0.825 AC: 34077 AN: 41290

American (AMR) AF: 0.581 AC: 8845 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2313 AN: 3470

East Asian (EAS) AF: 0.396 AC: 2042 AN: 5162

South Asian (SAS) AF: 0.530 AC: 2527 AN: 4766

European-Finnish (FIN) AF: 0.677 AC: 7082 AN: 10462

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 42981 AN: 67836

Other (OTH) AF: 0.663 AC: 1396 AN: 2106

Alfa AF: 0.657 Hom.: 3918

Bravo AF: 0.671

Asia WGS AF: 0.503 AC: 1750 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.25
DANN	Benign	0.43
PhyloP100		-2.4
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: rs2937345; hg19: chr2-48080260;