chr2-47820196-A-G

Position:

• chr2-47820196-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001190274.2(FBXO11):​c.1797+166T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 152,266 control chromosomes in the GnomAD database, including 249 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 0.056 (249 hom., cov: 32)
• Consequence: FBXO11 NM_001190274.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.553

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO11	NM_001190274.2	c.1797+166T>C		intron_variant		ENST00000403359.8	NP_001177203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO11	ENST00000403359.8	c.1797+166T>C		intron_variant		1	NM_001190274.2	ENSP00000384823

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8468 AN: 152148 Hom.: 247 Cov.: 32

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0428

Gnomad FIN AF: 0.0437

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0690

Gnomad OTH AF: 0.0511

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

GnomAD4 genome AF: 0.0557 AC: 8474 AN: 152266 Hom.: 249 Cov.: 32 AF XY: 0.0527 AC XY: 3925 AN XY: 74462

Gnomad4 AFR AF: 0.0519

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.0784

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.0437

Gnomad4 NFE AF: 0.0690

Gnomad4 OTH AF: 0.0506

Alfa AF: 0.0640 Hom.: 53

Bravo AF: 0.0538

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs4381823; hg19: chr2-48047335;