8-123513137-T-G

Position:

• chr8-123513137-T-G

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.651+61A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,543,220 control chromosomes in the GnomAD database, including 13,714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2085 hom., cov: 32)
  • Exomes 𝑓: 0.11 (11629 hom.)
• Consequence: FBXO32 NM_058229.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.762

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=-0.9).
• BP6: Variant 8-123513137-T-G is Benign according to our data. Variant chr8-123513137-T-G is described in ClinVar as [Benign]. Clinvar id is 1270505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO32	NM_058229.4	c.651+61A>C		intron_variant		ENST00000517956.5	NP_478136.1
FBXO32	NM_001242463.2	c.373-6563A>C		intron_variant			NP_001229392.1
FBXO32	NM_148177.3	c.216+61A>C		intron_variant			NP_680482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO32	ENST00000517956.5	c.651+61A>C		intron_variant		1	NM_058229.4	ENSP00000428205.1
FBXO32	ENST00000443022.2	c.373-6563A>C		intron_variant		1		ENSP00000390790.2
FBXO32	ENST00000287396.2	n.525+61A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22094 AN: 151968 Hom.: 2077 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.114 AC: 158932 AN: 1391134 Hom.: 11629 AF XY: 0.113 AC XY: 78325 AN XY: 694922

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.0831

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.0896

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.0999

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.145 AC: 22123 AN: 152086 Hom.: 2085 Cov.: 32 AF XY: 0.146 AC XY: 10879 AN XY: 74358

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0825

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.0973

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.135

Alfa AF: 0.104 Hom.: 975

Bravo AF: 0.154

Asia WGS AF: 0.260 AC: 901 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	-0.90
CADD	Benign	1.9
DANN	Benign	0.60

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: rs3739288; hg19: chr8-124525377;