3-33287943-G-T

Position:

• chr3-33287943-G-T

Variant summary

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

The NM_012157.5(FBXL2):​c.4-9721G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,272 control chromosomes in the GnomAD database, including 13,381 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 0.40 (13381 hom., cov: 31)
• Consequence: FBXL2 NM_012157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXL2	NM_012157.5	c.4-9721G>T		intron_variant		ENST00000484457.6	NP_036289.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL2	ENST00000484457.6	c.4-9721G>T		intron_variant		1	NM_012157.5	ENSP00000417601	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60262 AN: 151148 Hom.: 13326 Cov.: 31

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.399 AC: 60370 AN: 151272 Hom.: 13381 Cov.: 31 AF XY: 0.406 AC XY: 29997 AN XY: 73884

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.400

Alfa AF: 0.306 Hom.: 6494

Bravo AF: 0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.48

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: rs6777187; hg19: chr3-33329435;