rs10044254

Variant names:

• chr5-15783487-A-G
• rs10044254
• NM_012304.5:c.128-144403A>G

Variant summary

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

The NM_012304.5(FBXL7):​c.128-144403A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,100 control chromosomes in the GnomAD database, including 5,023 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 0.25 (5023 hom., cov: 32)
• Consequence: FBXL7 NM_012304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 11 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012304.5. 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
	FBXL7	NM_012304.5	MANE Select	c.128-144403A>G		intron	N/A	NP_036436.1	Q9UJT9-1
	FBXL7	NM_001278317.2		c.-14-144403A>G		intron	N/A	NP_001265246.1	Q9UJT9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL7	ENST00000504595.2	TSL:1 MANE Select	c.128-144403A>G		intron	N/A	ENSP00000423630.1	Q9UJT9-1
	FBXL7	ENST00000510662.1	TSL:1	c.-14-144403A>G		intron	N/A	ENSP00000425184.1	Q9UJT9-2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37741 AN: 151982 Hom.: 5017 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.248 AC: 37776 AN: 152100 Hom.: 5023 Cov.: 32 AF XY: 0.247 AC XY: 18384 AN XY: 74356

African (AFR) AF: 0.345 AC: 14305 AN: 41478

American (AMR) AF: 0.253 AC: 3876 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3470

East Asian (EAS) AF: 0.105 AC: 545 AN: 5170

South Asian (SAS) AF: 0.122 AC: 587 AN: 4816

European-Finnish (FIN) AF: 0.223 AC: 2362 AN: 10588

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14861 AN: 67970

Other (OTH) AF: 0.233 AC: 491 AN: 2110

Alfa AF: 0.223 Hom.: 2161

Bravo AF: 0.253

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.86
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: rs10044254; hg19: chr5-15783596;