chr8-123504573-G-A

Position:

• chr8-123504573-G-A

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.978+31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 1,599,220 control chromosomes in the GnomAD database, including 6,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1886 hom., cov: 31)
  • Exomes 𝑓: 0.070 (4908 hom.)
• Consequence: FBXO32 NM_058229.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.22

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=-0.67).
• BP6: Variant 8-123504573-G-A is Benign according to our data. Variant chr8-123504573-G-A is described in ClinVar as [Benign]. Clinvar id is 1282066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO32	NM_058229.4	c.978+31C>T		intron_variant		ENST00000517956.5	NP_478136.1
FBXO32	NM_001242463.2	c.699+31C>T		intron_variant			NP_001229392.1
FBXO32	NM_148177.3	c.543+31C>T		intron_variant			NP_680482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO32	ENST00000517956.5	c.978+31C>T		intron_variant		1	NM_058229.4	ENSP00000428205.1
FBXO32	ENST00000443022.2	c.699+31C>T		intron_variant		1		ENSP00000390790.2
FBXO32	ENST00000287396.2	n.852+31C>T		intron_variant		1
FBXO32	ENST00000524000.5	n.378+31C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18788 AN: 151836 Hom.: 1878 Cov.: 31

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0856

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00914

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0690

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.0657 AC: 15742 AN: 239704 Hom.: 1034 AF XY: 0.0597 AC XY: 7735 AN XY: 129516

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.0477

Gnomad ASJ exome AF: 0.0497

Gnomad EAS exome AF: 0.000170

Gnomad SAS exome AF: 0.00869

Gnomad FIN exome AF: 0.0552

Gnomad NFE exome AF: 0.0680

Gnomad OTH exome AF: 0.0612

GnomAD4 exome AF: 0.0702 AC: 101640 AN: 1447266 Hom.: 4908 Cov.: 31 AF XY: 0.0678 AC XY: 48739 AN XY: 719190

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.0534

Gnomad4 ASJ exome AF: 0.0477

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.00979

Gnomad4 FIN exome AF: 0.0546

Gnomad4 NFE exome AF: 0.0723

Gnomad4 OTH exome AF: 0.0752

GnomAD4 genome AF: 0.124 AC: 18826 AN: 151954 Hom.: 1886 Cov.: 31 AF XY: 0.119 AC XY: 8855 AN XY: 74274

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.0855

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.00894

Gnomad4 FIN AF: 0.0472

Gnomad4 NFE AF: 0.0690

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0845 Hom.: 205

Bravo AF: 0.135

Asia WGS AF: 0.0220 AC: 79 AN: 3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73330050; hg19: chr8-124516813;