8-123514523-T-C

Position:

• chr8-123514523-T-C

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.373-190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,246 control chromosomes in the GnomAD database, including 2,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2503 hom., cov: 32)
• Consequence: FBXO32 NM_058229.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.176

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=-0.86).
• BP6: Variant 8-123514523-T-C is Benign according to our data. Variant chr8-123514523-T-C is described in ClinVar as [Benign]. Clinvar id is 1278480.Status of the report is criteria_provided_single_submitter, 1 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.373-190A>G		intron_variant		ENST00000517956.5	NP_478136.1
FBXO32	NM_001242463.2	c.373-7949A>G		intron_variant			NP_001229392.1
FBXO32	NM_148177.3	c.-63-190A>G		intron_variant			NP_680482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO32	ENST00000517956.5	c.373-190A>G		intron_variant		1	NM_058229.4	ENSP00000428205.1
FBXO32	ENST00000443022.2	c.373-7949A>G		intron_variant		1		ENSP00000390790.2
FBXO32	ENST00000287396.2	n.247-190A>G		intron_variant		1
FBXO32	ENST00000521719.5	n.548-190A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24095 AN: 152128 Hom.: 2493 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0757

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.0982

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.158 AC: 24127 AN: 152246 Hom.: 2503 Cov.: 32 AF XY: 0.159 AC XY: 11807 AN XY: 74434

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0757

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.0983

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.142

Alfa AF: 0.121 Hom.: 356

Bravo AF: 0.168

Asia WGS AF: 0.263 AC: 914 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 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	10
DANN	Benign	0.59

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: rs2294089; hg19: chr8-124526763;