rs12659622

Variant names:

• chr5-15618072-G-A
• rs12659622
• NM_012304.5:c.127+2000G>A

Variant summary

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

The NM_012304.5(FBXL7):​c.127+2000G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 152,064 control chromosomes in the GnomAD database, including 621 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 0.085 (621 hom., cov: 32)
• Consequence: FBXL7 NM_012304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 4 publications found

Genes affected

FBXL7 (HGNC:13604): (F-box and leucine rich repeat protein 7) This gene encodes a member of the F-box protein family which is characterized by a 42-48 amino acid motif, the F-box, which binds to the S-phase kinase-associated protein 1 (Skp1) protein. The F-box proteins constitute one of the four subunits of E3 ubiquitin protein ligases called SCFs (SKP1-Cul1-F-box), which play a role in phosphorylation-dependent ubiquitination of proteins. The F-box proteins are divided into 3 subfamilies based on the other domain in the protein: F-box proteins that also have a WD-40 domain (Fbws subfamily), F-box proteins that also have leucine-rich repeats (Fbls subfamily) and F-box proteins that contain other motifs or lack known protein-interaction domains (Fbxs subfamily). The protein encoded by this gene belongs to the Fbls subfamily. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

ENSG00000250250 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL7	NM_012304.5	c.127+2000G>A		intron_variant	Intron 2 of 3	ENST00000504595.2	NP_036436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL7	ENST00000504595.2	c.127+2000G>A		intron_variant	Intron 2 of 3	1	NM_012304.5	ENSP00000423630.1

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12890 AN: 151946 Hom.: 622 Cov.: 32

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0860

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

GnomAD4 genome AF: 0.0847 AC: 12887 AN: 152064 Hom.: 621 Cov.: 32 AF XY: 0.0845 AC XY: 6282 AN XY: 74344

African (AFR) AF: 0.0402 AC: 1666 AN: 41474

American (AMR) AF: 0.0876 AC: 1338 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3470

East Asian (EAS) AF: 0.0906 AC: 468 AN: 5164

South Asian (SAS) AF: 0.133 AC: 642 AN: 4820

European-Finnish (FIN) AF: 0.0741 AC: 784 AN: 10574

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7383 AN: 67974

Other (OTH) AF: 0.0856 AC: 180 AN: 2104

Alfa AF: 0.0974 Hom.: 1315

Bravo AF: 0.0820

Asia WGS AF: 0.114 AC: 395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.69
PhyloP100		0.14
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: rs12659622; hg19: chr5-15618181;