rs4374757

Variant names:

• chr5-15719241-A-G
• rs4374757
• NM_012304.5:c.127+103169A>G

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+103169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,106 control chromosomes in the GnomAD database, including 5,355 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 0.24 (5355 hom., cov: 32)
• Consequence: FBXL7 NM_012304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL7	NM_012304.5	c.127+103169A>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+103169A>G		intron_variant	Intron 2 of 3	1	NM_012304.5	ENSP00000423630.1
FBXL7	ENST00000510662.1	c.-15+103169A>G		intron_variant	Intron 2 of 3	1		ENSP00000425184.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36193 AN: 151988 Hom.: 5357 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.238 AC: 36189 AN: 152106 Hom.: 5355 Cov.: 32 AF XY: 0.240 AC XY: 17815 AN XY: 74350

African (AFR) AF: 0.0623 AC: 2589 AN: 41552

American (AMR) AF: 0.284 AC: 4332 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1401 AN: 3472

East Asian (EAS) AF: 0.233 AC: 1205 AN: 5168

South Asian (SAS) AF: 0.379 AC: 1823 AN: 4816

European-Finnish (FIN) AF: 0.276 AC: 2917 AN: 10574

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20978 AN: 67938

Other (OTH) AF: 0.250 AC: 528 AN: 2112

Alfa AF: 0.292 Hom.: 11394

Bravo AF: 0.232

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.17
DANN	Benign	0.60
PhyloP100		-0.75
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: rs4374757; hg19: chr5-15719350;