chr5-15589808-G-A

Variant names:

• chr5-15589808-G-A
• rs10520818
• NM_012304.5:c.38-26175G>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.38-26175G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,076 control chromosomes in the GnomAD database, including 1,560 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 0.14 (1560 hom., cov: 31)
• Consequence: FBXL7 NM_012304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609
• Publications: 2 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]

ENSG00000250250 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL7	NM_012304.5	c.38-26175G>A		intron_variant	Intron 1 of 3	ENST00000504595.2	NP_036436.1
FBXL7	NM_001278317.2	c.-104-26175G>A		intron_variant	Intron 1 of 3		NP_001265246.1
FBXL7	XM_017009262.3	c.22+8996G>A		intron_variant	Intron 1 of 3		XP_016864751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL7	ENST00000504595.2	c.38-26175G>A		intron_variant	Intron 1 of 3	1	NM_012304.5	ENSP00000423630.1
FBXL7	ENST00000510662.1	c.-104-26175G>A		intron_variant	Intron 1 of 3	1		ENSP00000425184.1
ENSG00000250250	ENST00000757355.1	n.263+17352C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21265 AN: 151958 Hom.: 1556 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.140 AC: 21282 AN: 152076 Hom.: 1560 Cov.: 31 AF XY: 0.144 AC XY: 10671 AN XY: 74322

African (AFR) AF: 0.166 AC: 6904 AN: 41472

American (AMR) AF: 0.139 AC: 2126 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3470

East Asian (EAS) AF: 0.145 AC: 745 AN: 5148

South Asian (SAS) AF: 0.232 AC: 1118 AN: 4816

European-Finnish (FIN) AF: 0.159 AC: 1678 AN: 10586

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7919 AN: 67978

Other (OTH) AF: 0.126 AC: 266 AN: 2110

Alfa AF: 0.126 Hom.: 855

Bravo AF: 0.137

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.70
DANN	Benign	0.44
PhyloP100		-0.61
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: rs10520818; hg19: chr5-15589917;