rs12652447

Variant names:

• chr5-15674526-G-A
• rs12652447
• NM_012304.5:c.127+58454G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-15674526-G-A
• chr5-15674526-G-T

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+58454G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,000 control chromosomes in the GnomAD database, including 16,863 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 0.46 (16863 hom., cov: 32)
• Consequence: FBXL7 NM_012304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 7 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL7	NM_012304.5	c.127+58454G>A		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+58454G>A		intron_variant	Intron 2 of 3	1	NM_012304.5	ENSP00000423630.1
FBXL7	ENST00000510662.1	c.-15+58454G>A		intron_variant	Intron 2 of 3	1		ENSP00000425184.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70397 AN: 151882 Hom.: 16833 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.464 AC: 70473 AN: 152000 Hom.: 16863 Cov.: 32 AF XY: 0.458 AC XY: 34068 AN XY: 74304

African (AFR) AF: 0.582 AC: 24122 AN: 41466

American (AMR) AF: 0.414 AC: 6322 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1421 AN: 3468

East Asian (EAS) AF: 0.581 AC: 2995 AN: 5154

South Asian (SAS) AF: 0.388 AC: 1869 AN: 4818

European-Finnish (FIN) AF: 0.382 AC: 4024 AN: 10538

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28292 AN: 67964

Other (OTH) AF: 0.457 AC: 966 AN: 2112

Alfa AF: 0.429 Hom.: 45119

Bravo AF: 0.472

Asia WGS AF: 0.477 AC: 1655 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		0.051
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: rs12652447; hg19: chr5-15674635;