chr8-123530245-T-C

Variant names:

• chr8-123530245-T-C
• rs7830622
• NM_058229.4:c.372+1653A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

FBXO32 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058229.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO32	NM_058229.4	MANE Select	c.372+1653A>G		intron	N/A	NP_478136.1	Q969P5-1
	FBXO32	NM_001242463.2		c.372+1653A>G		intron	N/A	NP_001229392.1	Q969P5-2
	FBXO32	NM_148177.3		c.-64+1653A>G		intron	N/A	NP_680482.1	Q0VAQ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO32	ENST00000517956.5	TSL:1 MANE Select	c.372+1653A>G		intron	N/A	ENSP00000428205.1	Q969P5-1
	FBXO32	ENST00000443022.2	TSL:1	c.372+1653A>G		intron	N/A	ENSP00000390790.2	Q969P5-2
	FBXO32	ENST00000287396.2	TSL:1	n.246+1653A>G		intron	N/A

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

African (AFR) AF: 0.0570 AC: 2367 AN: 41544

American (AMR) AF: 0.0319 AC: 488 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3468

East Asian (EAS) AF: 0.140 AC: 723 AN: 5170

South Asian (SAS) AF: 0.0573 AC: 275 AN: 4800

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10624

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0352 AC: 2396 AN: 68020

Other (OTH) AF: 0.0444 AC: 94 AN: 2116

Alfa AF: 0.0362 Hom.: 233

Bravo AF: 0.0451

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		0.62
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: rs7830622; hg19: chr8-124542485;