rs75002042

chr5-15669858-T-Achr5-15669858-T-C

Variant summary

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

The NM_012304.5(FBXL7):c.127+53786T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 152,218 control chromosomes in the GnomAD database, including 1,235 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 0.078 (1235 hom., cov: 32)
• Consequence: FBXL7 NM_012304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXL7	NM_012304.5	c.127+53786T>A		intron_variant		ENST00000504595.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXL7	ENST00000504595.2	c.127+53786T>A		intron_variant		1	NM_012304.5	P1
FBXL7	ENST00000510662.1	c.-15+53786T>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11803 AN: 152100 Hom.: 1233 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.00735

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00931

Gnomad OTH AF: 0.0569

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

GnomAD4 genome AF: 0.0776 AC: 11817 AN: 152218 Hom.: 1235 Cov.: 32 AF XY: 0.0766 AC XY: 5698 AN XY: 74416

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.0321

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.0429

Gnomad4 FIN AF: 0.00735

Gnomad4 NFE AF: 0.00932

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0113 Hom.: 16

Bravo AF: 0.0865

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.82
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs75002042; hg19: chr5-15669967;