rs1864220

Positions:

• chr5-15621985-A-C
• chr5-15621985-A-G

Variant summary

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

The NM_012304.5(FBXL7):​c.127+5913A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 152,274 control chromosomes in the GnomAD database, including 821 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 0.098 (821 hom., cov: 33)
• Consequence: FBXL7 NM_012304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.792

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXL7	NM_012304.5	c.127+5913A>C		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+5913A>C		intron_variant		1	NM_012304.5	ENSP00000423630	P1
FBXL7	ENST00000510662.1	c.-15+5913A>C		intron_variant		1		ENSP00000425184

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 14955 AN: 152158 Hom.: 822 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0699

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.0862

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0893

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0982 AC: 14955 AN: 152274 Hom.: 821 Cov.: 33 AF XY: 0.0952 AC XY: 7086 AN XY: 74452

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.0860

Gnomad4 SAS AF: 0.0940

Gnomad4 FIN AF: 0.0393

Gnomad4 NFE AF: 0.0893

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0933 Hom.: 107

Bravo AF: 0.103

Asia WGS AF: 0.0900 AC: 311 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.1
DANN	Benign	0.91

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: rs1864220; hg19: chr5-15622094;