3-33287943-G-T

Variant names:

• chr3-33287943-G-T
• rs6777187
• NM_012157.5:c.4-9721G>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.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
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL2	NM_012157.5	MANE Select	c.4-9721G>T		intron	N/A	NP_036289.3
	FBXL2	NM_001349316.2		c.4-9721G>T		intron	N/A	NP_001336245.1
	FBXL2	NM_001349319.2		c.-331-9721G>T		intron	N/A	NP_001336248.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL2	ENST00000484457.6	TSL:1 MANE Select	c.4-9721G>T		intron	N/A	ENSP00000417601.1	Q9UKC9-1
	FBXL2	ENST00000898646.1		c.4-9721G>T		intron	N/A	ENSP00000568705.1
	FBXL2	ENST00000898645.1		c.4-9721G>T		intron	N/A	ENSP00000568704.1

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

African (AFR) AF: 0.544 AC: 22445 AN: 41228

American (AMR) AF: 0.519 AC: 7877 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1028 AN: 3458

East Asian (EAS) AF: 0.600 AC: 3077 AN: 5128

South Asian (SAS) AF: 0.408 AC: 1957 AN: 4796

European-Finnish (FIN) AF: 0.355 AC: 3693 AN: 10414

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19199 AN: 67770

Other (OTH) AF: 0.400 AC: 836 AN: 2092

Alfa AF: 0.311 Hom.: 7531

Bravo AF: 0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.48
PhyloP100		0.019
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: rs6777187; hg19: chr3-33329435;