rs7830622

chr8-123530245-T-C

Variant summary

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

The NM_058229.4(FBXO32):c.372+1653A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 152,244 control chromosomes in the GnomAD database, including 196 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 0.044 (196 hom., cov: 32)
• Consequence: FBXO32 NM_058229.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621

Genes affected

FBXO32 (HGNC:16731): (F-box protein 32) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and contains an F-box domain. This protein is highly expressed during muscle atrophy, whereas mice deficient in this gene were found to be resistant to atrophy. This protein is thus a potential drug target for the treatment of muscle atrophy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO32	NM_058229.4	c.372+1653A>G		intron_variant		ENST00000517956.5
FBXO32	NM_001242463.2	c.372+1653A>G		intron_variant
FBXO32	NM_148177.3	c.-64+1653A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO32	ENST00000517956.5	c.372+1653A>G		intron_variant		1	NM_058229.4	P1

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6626 AN: 152126 Hom.: 198 Cov.: 32

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0319

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0568

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0444

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

GnomAD4 genome AF: 0.0436 AC: 6631 AN: 152244 Hom.: 196 Cov.: 32 AF XY: 0.0424 AC XY: 3155 AN XY: 74432

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.0319

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.0573

Gnomad4 FIN AF: 0.0132

Gnomad4 NFE AF: 0.0352

Gnomad4 OTH AF: 0.0444

Alfa AF: 0.0359 Hom.: 168

Bravo AF: 0.0451

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	14
Dann	Benign	0.75

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: rs7830622; hg19: chr8-124542485;