rs2047681

Variant names:

• chr2-47829092-G-A
• rs2047681
• NM_001190274.2:c.1398+3257C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-47829092-G-A
• chr2-47829092-G-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.1398+3257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 151,948 control chromosomes in the GnomAD database, including 57,647 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 0.87 (57647 hom., cov: 28)
• Consequence: FBXO11 NM_001190274.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO11	NM_001190274.2	c.1398+3257C>T		intron_variant	Intron 11 of 22	ENST00000403359.8	NP_001177203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO11	ENST00000403359.8	c.1398+3257C>T		intron_variant	Intron 11 of 22	1	NM_001190274.2	ENSP00000384823.4

Frequencies

GnomAD3 genomes AF: 0.869 AC: 131967 AN: 151830 Hom.: 57580 Cov.: 28

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.869 AC: 132095 AN: 151948 Hom.: 57647 Cov.: 28 AF XY: 0.874 AC XY: 64872 AN XY: 74252

African (AFR) AF: 0.904 AC: 37461 AN: 41426

American (AMR) AF: 0.890 AC: 13592 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2973 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5148 AN: 5152

South Asian (SAS) AF: 0.955 AC: 4586 AN: 4804

European-Finnish (FIN) AF: 0.881 AC: 9280 AN: 10536

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.827 AC: 56220 AN: 67982

Other (OTH) AF: 0.860 AC: 1815 AN: 2110

Alfa AF: 0.862 Hom.: 7042

Bravo AF: 0.869

Asia WGS AF: 0.959 AC: 3332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.17
PhyloP100		-0.87
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: rs2047681; hg19: chr2-48056231;