rs4571472

Variant names:

• chr5-15721251-A-G
• rs4571472
• NM_012304.5:c.127+105179A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-15721251-A-G
• chr5-15721251-A-T

Variant summary

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

The NM_012304.5(FBXL7):​c.127+105179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,834 control chromosomes in the GnomAD database, including 29,568 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 0.62 (29568 hom., cov: 31)
• Consequence: FBXL7 NM_012304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL7	NM_012304.5	c.127+105179A>G		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+105179A>G		intron_variant	Intron 2 of 3	1	NM_012304.5	ENSP00000423630.1
FBXL7	ENST00000510662.1	c.-15+105179A>G		intron_variant	Intron 2 of 3	1		ENSP00000425184.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94178 AN: 151716 Hom.: 29568 Cov.: 31

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.621 AC: 94218 AN: 151834 Hom.: 29568 Cov.: 31 AF XY: 0.623 AC XY: 46227 AN XY: 74174

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.632

Alfa AF: 0.619 Hom.: 11805

Bravo AF: 0.618

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.39

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: rs4571472; hg19: chr5-15721360;