5-15628952-G-A

Variant names:

• chr5-15628952-G-A
• rs12757
• NM_012304.5:c.127+12880G>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+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
• 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL7	NM_012304.5	MANE Select	c.127+12880G>A		intron	N/A	NP_036436.1
	FBXL7	NM_001278317.2		c.-15+12880G>A		intron	N/A	NP_001265246.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL7	ENST00000504595.2	TSL:1 MANE Select	c.127+12880G>A		intron	N/A	ENSP00000423630.1
	FBXL7	ENST00000510662.1	TSL:1	c.-15+12880G>A		intron	N/A	ENSP00000425184.1

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

African (AFR) AF: 0.219 AC: 9050 AN: 41346

American (AMR) AF: 0.253 AC: 3851 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3468

East Asian (EAS) AF: 0.0912 AC: 468 AN: 5134

South Asian (SAS) AF: 0.208 AC: 998 AN: 4798

European-Finnish (FIN) AF: 0.223 AC: 2340 AN: 10482

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19611 AN: 67900

Other (OTH) AF: 0.270 AC: 565 AN: 2094

Alfa AF: 0.271 Hom.: 3225

Bravo AF: 0.253

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.23
PhyloP100		0.20
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: rs12757; hg19: chr5-15629061;