chr3-33377930-C-T

Variant names:

• chr3-33377930-C-T
• rs2291897
• NM_012157.5:c.850-173C>T

Variant summary

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

The NM_012157.5(FBXL2):​c.850-173C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,068 control chromosomes in the GnomAD database, including 5,927 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 0.26 (5927 hom., cov: 32)
• Consequence: FBXL2 NM_012157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533
• Publications: 12 publications found

Genes affected

FBXL2 (HGNC:13598): (F-box and leucine rich repeat protein 2) 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 Fbls class and, in addition to an F-box, contains 12 tandem leucine-rich repeats. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012157.5. 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
	FBXL2	NM_012157.5	MANE Select	c.850-173C>T		intron	N/A	NP_036289.3
	FBXL2	NM_001349316.2		c.850-173C>T		intron	N/A	NP_001336245.1
	FBXL2	NM_001349319.2		c.535-173C>T		intron	N/A	NP_001336248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL2	ENST00000484457.6	TSL:1 MANE Select	c.850-173C>T		intron	N/A	ENSP00000417601.1
	FBXL2	ENST00000283627.10	TSL:5	n.862-173C>T		intron	N/A
	FBXL2	ENST00000421391.5	TSL:2	n.*479-173C>T		intron	N/A	ENSP00000408895.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39047 AN: 151950 Hom.: 5900 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.257 AC: 39110 AN: 152068 Hom.: 5927 Cov.: 32 AF XY: 0.263 AC XY: 19572 AN XY: 74326

African (AFR) AF: 0.365 AC: 15140 AN: 41468

American (AMR) AF: 0.344 AC: 5247 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3470

East Asian (EAS) AF: 0.468 AC: 2411 AN: 5154

South Asian (SAS) AF: 0.237 AC: 1142 AN: 4828

European-Finnish (FIN) AF: 0.268 AC: 2829 AN: 10566

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11031 AN: 67990

Other (OTH) AF: 0.257 AC: 544 AN: 2114

Alfa AF: 0.197 Hom.: 10962

Bravo AF: 0.271

Asia WGS AF: 0.387 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.35
PhyloP100		0.53
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: rs2291897; hg19: chr3-33419422; COSMIC: COSV52142312; COSMIC: COSV52142312;