rs13087731

chr3-33387790-T-C

Variant summary

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

The NM_012157.5(FBXL2):c.*2182T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,046 control chromosomes in the GnomAD database, including 11,560 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 0.38 (11546 hom., cov: 31)
  • Exomes 𝑓: 0.38 (14 hom.)
• Consequence: FBXL2 NM_012157.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXL2	NM_012157.5	c.*2182T>C		3_prime_UTR_variant	15/15	ENST00000484457.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXL2	ENST00000484457.6	c.*2182T>C		3_prime_UTR_variant	15/15	1	NM_012157.5	P1
FBXL2	ENST00000463736.5	n.1214+2062T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58335 AN: 151768 Hom.: 11519 Cov.: 31

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.380 AC: 60 AN: 158 Hom.: 14 Cov.: 0 AF XY: 0.405 AC XY: 47 AN XY: 116

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 0.667

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.385 AC: 58406 AN: 151888 Hom.: 11546 Cov.: 31 AF XY: 0.385 AC XY: 28574 AN XY: 74240

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.397

Alfa AF: 0.360 Hom.: 9512

Bravo AF: 0.399

Asia WGS AF: 0.450 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.9
Dann	Benign	0.32

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: rs13087731; hg19: chr3-33429282;