rs330787

Variant names:

• chr2-47814238-A-G
• rs330787
• NM_001190274.2:c.2007-371T>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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 20 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=-0.99).
• 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 rank	MANE	Protein	UniProt
FBXO11	NM_001190274.2	c.2007-371T>C		intron_variant	Intron 16 of 22	ENST00000403359.8	NP_001177203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO11	ENST00000403359.8	c.2007-371T>C		intron_variant	Intron 16 of 22	1	NM_001190274.2	ENSP00000384823.4

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104096 AN: 151816 Hom.: 36324 Cov.: 30

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

African (AFR) AF: 0.813 AC: 871 AN: 1072

American (AMR) AF: 0.604 AC: 1918 AN: 3176

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 556 AN: 904

East Asian (EAS) AF: 0.442 AC: 1065 AN: 2410

South Asian (SAS) AF: 0.617 AC: 2631 AN: 4266

European-Finnish (FIN) AF: 0.617 AC: 495 AN: 802

Middle Eastern (MID) AF: 0.680 AC: 68 AN: 100

European-Non Finnish (NFE) AF: 0.616 AC: 12489 AN: 20262

Other (OTH) AF: 0.637 AC: 1116 AN: 1752

GnomAD4 genome AF: 0.686 AC: 104229 AN: 151934 Hom.: 36396 Cov.: 30 AF XY: 0.684 AC XY: 50754 AN XY: 74234

African (AFR) AF: 0.834 AC: 34544 AN: 41442

American (AMR) AF: 0.640 AC: 9761 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2263 AN: 3472

East Asian (EAS) AF: 0.469 AC: 2428 AN: 5176

South Asian (SAS) AF: 0.597 AC: 2867 AN: 4804

European-Finnish (FIN) AF: 0.652 AC: 6847 AN: 10498

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43302 AN: 67966

Other (OTH) AF: 0.684 AC: 1444 AN: 2112

Alfa AF: 0.646 Hom.: 53759

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
PhyloP100		-0.0040
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: rs330787; hg19: chr2-48041377;