8-123506290-A-G

Position:

• chr8-123506290-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_058229.4(FBXO32):​c.834+102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,287,382 control chromosomes in the GnomAD database, including 59,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (12977 hom., cov: 32)
  • Exomes 𝑓: 0.27 (46212 hom.)
• Consequence: FBXO32 NM_058229.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.236

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-123506290-A-G is Benign according to our data. Variant chr8-123506290-A-G is described in ClinVar as [Benign]. Clinvar id is 1260578.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO32	NM_058229.4	c.834+102T>C		intron_variant		ENST00000517956.5	NP_478136.1
FBXO32	NM_001242463.2	c.555+102T>C		intron_variant			NP_001229392.1
FBXO32	NM_148177.3	c.399+102T>C		intron_variant			NP_680482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO32	ENST00000517956.5	c.834+102T>C		intron_variant		1	NM_058229.4	ENSP00000428205.1
FBXO32	ENST00000443022.2	c.555+102T>C		intron_variant		1		ENSP00000390790.2
FBXO32	ENST00000287396.2	n.708+102T>C		intron_variant		1
FBXO32	ENST00000524000.5	n.234+102T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56739 AN: 151926 Hom.: 12942 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.267 AC: 303628 AN: 1135338 Hom.: 46212 AF XY: 0.264 AC XY: 150012 AN XY: 569224

Gnomad4 AFR exome AF: 0.622

Gnomad4 AMR exome AF: 0.485

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.601

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.289

GnomAD4 genome AF: 0.374 AC: 56832 AN: 152044 Hom.: 12977 Cov.: 32 AF XY: 0.372 AC XY: 27671 AN XY: 74332

Gnomad4 AFR AF: 0.610

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.369

Alfa AF: 0.286 Hom.: 3864

Bravo AF: 0.407

Asia WGS AF: 0.372 AC: 1296 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.76

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: rs10093411; hg19: chr8-124518530; COSMIC: COSV54891297;