rs12757

Positions:

• chr5-15628952-G-A
• chr5-15628952-G-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+12880G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,628 control chromosomes in the GnomAD database, including 5,050 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 (5050 hom., cov: 31)
• Consequence: FBXL7 NM_012304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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 (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXL7	NM_012304.5	c.127+12880G>A		intron_variant		ENST00000504595.2	NP_036436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL7	ENST00000504595.2	c.127+12880G>A		intron_variant		1	NM_012304.5	ENSP00000423630	P1
FBXL7	ENST00000510662.1	c.-15+12880G>A		intron_variant		1		ENSP00000425184

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38279 AN: 151510 Hom.: 5053 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.0913

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.253 AC: 38298 AN: 151628 Hom.: 5050 Cov.: 31 AF XY: 0.246 AC XY: 18245 AN XY: 74044

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.0912

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.270

Alfa AF: 0.270 Hom.: 2893

Bravo AF: 0.253

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.23

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: rs12757; hg19: chr5-15629061;