2-47845978-C-T

Variant names:

• chr2-47845978-C-T
• rs2134056
• NM_001190274.2:c.233-6209G>A

Variant summary

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

The NM_001190274.2(FBXO11):​c.233-6209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 151,790 control chromosomes in the GnomAD database, including 1,811 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 0.15 (1811 hom., cov: 32)
• Consequence: FBXO11 NM_001190274.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 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.233-6209G>A		intron	N/A	NP_001177203.1
	FBXO11	NM_001374325.1		c.-20-6209G>A		intron	N/A	NP_001361254.1
	FBXO11	NM_025133.4		c.-20-6209G>A		intron	N/A	NP_079409.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO11	ENST00000403359.8	TSL:1 MANE Select	c.233-6209G>A		intron	N/A	ENSP00000384823.4
	FBXO11	ENST00000402508.5	TSL:1	c.-20-6209G>A		intron	N/A	ENSP00000385398.1
	FBXO11	ENST00000492225.5	TSL:1	n.81-6209G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22646 AN: 151678 Hom.: 1806 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0992

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.149 AC: 22674 AN: 151790 Hom.: 1811 Cov.: 32 AF XY: 0.146 AC XY: 10784 AN XY: 74116

African (AFR) AF: 0.149 AC: 6151 AN: 41414

American (AMR) AF: 0.0991 AC: 1512 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 390 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5170

South Asian (SAS) AF: 0.0703 AC: 338 AN: 4810

European-Finnish (FIN) AF: 0.199 AC: 2071 AN: 10422

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.174 AC: 11789 AN: 67940

Other (OTH) AF: 0.147 AC: 309 AN: 2106

Alfa AF: 0.146 Hom.: 964

Bravo AF: 0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.1
DANN	Benign	0.51
PhyloP100		0.20
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: rs2134056; hg19: chr2-48073117;