rs4952896

Variant names:

• chr2-47888987-G-A
• rs4952896
• NM_001190274.2:c.232+16502C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-47888987-G-A
• chr2-47888987-G-T

Variant summary

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

The NM_001190274.2(FBXO11):​c.232+16502C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,186 control chromosomes in the GnomAD database, including 48,330 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 0.79 (48330 hom., cov: 33)
• Consequence: FBXO11 NM_001190274.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO11	NM_001190274.2	MANE Select	c.232+16502C>T		intron	N/A	NP_001177203.1
	FBXO11	NM_001374325.1		c.-21+16106C>T		intron	N/A	NP_001361254.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO11	ENST00000403359.8	TSL:1 MANE Select	c.232+16502C>T		intron	N/A	ENSP00000384823.4
	FBXO11	ENST00000492225.5	TSL:1	n.80+16502C>T		intron	N/A
	FBXO11	ENST00000683894.1		c.-21+16502C>T		intron	N/A	ENSP00000507789.1

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120218 AN: 152068 Hom.: 48278 Cov.: 33

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.791 AC: 120319 AN: 152186 Hom.: 48330 Cov.: 33 AF XY: 0.788 AC XY: 58587 AN XY: 74382

African (AFR) AF: 0.939 AC: 39000 AN: 41544

American (AMR) AF: 0.728 AC: 11127 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2603 AN: 3472

East Asian (EAS) AF: 0.884 AC: 4584 AN: 5188

South Asian (SAS) AF: 0.774 AC: 3732 AN: 4820

European-Finnish (FIN) AF: 0.656 AC: 6924 AN: 10560

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

European-Non Finnish (NFE) AF: 0.733 AC: 49872 AN: 68000

Other (OTH) AF: 0.763 AC: 1611 AN: 2112

Alfa AF: 0.752 Hom.: 71987

Bravo AF: 0.803

Asia WGS AF: 0.832 AC: 2891 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.6
DANN	Benign	0.49
PhyloP100		0.42
PromoterAI		-0.0085	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4952896; hg19: chr2-48116126; COSMIC: COSV57024883; COSMIC: COSV57024883;