chr8-123504971-A-C

Position:

• chr8-123504971-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_058229.4(FBXO32):​c.835-224T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0995 in 152,166 control chromosomes in the GnomAD database, including 1,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.10 (1046 hom., cov: 32)
• Consequence: FBXO32 NM_058229.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.422

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-123504971-A-C is Benign according to our data. Variant chr8-123504971-A-C is described in ClinVar as [Benign]. Clinvar id is 1237383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO32	NM_058229.4	c.835-224T>G		intron_variant		ENST00000517956.5	NP_478136.1
FBXO32	NM_001242463.2	c.556-224T>G		intron_variant			NP_001229392.1
FBXO32	NM_148177.3	c.400-224T>G		intron_variant			NP_680482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO32	ENST00000517956.5	c.835-224T>G		intron_variant		1	NM_058229.4	ENSP00000428205.1
FBXO32	ENST00000443022.2	c.556-224T>G		intron_variant		1		ENSP00000390790.2
FBXO32	ENST00000287396.2	n.709-224T>G		intron_variant		1
FBXO32	ENST00000524000.5	n.235-224T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15113 AN: 152048 Hom.: 1039 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.0478

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.0995 AC: 15146 AN: 152166 Hom.: 1046 Cov.: 32 AF XY: 0.102 AC XY: 7568 AN XY: 74418

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.0478

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.0641

Gnomad4 FIN AF: 0.0562

Gnomad4 NFE AF: 0.0508

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0366 Hom.: 27

Bravo AF: 0.129

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.69

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: rs55994600; hg19: chr8-124517211; COSMIC: COSV54890063;