Genetic Variant NM_058229.4:c.372+1653A>G (chr8-123530245-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_058229.4(FBXO32):c.372+1653A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 152,244 control chromosomes in the GnomAD database, including 196 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.044 ( 196 hom., cov: 32)

Consequence

FBXO32
NM_058229.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.621

Publications

8 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

FBXO32 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FBXO32	NM_058229.4 link	c.372+1653A>G	intron_variant	Intron 4 of 8	ENST00000517956.5	NP_478136.1	Q969P5-1A0A024R9F3
FBXO32	NM_001242463.2 link	c.372+1653A>G	intron_variant	Intron 4 of 6		NP_001229392.1	Q969P5-2
FBXO32	NM_148177.3 link	c.-64+1653A>G	intron_variant	Intron 1 of 5		NP_680482.1	Q0VAQ6Q498Y9I6L984

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO32	ENST00000517956.5 link	c.372+1653A>G		intron_variant	Intron 4 of 8	1	NM_058229.4	ENSP00000428205.1		Q969P5-1

Frequencies

GnomAD3 genomes

AF:

0.0436

AC:

6626

AN:

152126

Hom.:

198

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0570

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0319

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.0568

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0352

Gnomad OTH

AF:

0.0444

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

GnomAD4 genome

AF:

0.0436

AC:

6631

AN:

152244

Hom.:

196

Cov.:

AF XY:

0.0424

AC XY:

3155

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0570

AC:

2367

AN:

41544

American (AMR)

AF:

0.0319

AC:

488

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0343

AC:

119

AN:

3468

East Asian (EAS)

AF:

0.140

AC:

723

AN:

5170

South Asian (SAS)

AF:

0.0573

AC:

275

AN:

4800

European-Finnish (FIN)

AF:

0.0132

AC:

140

AN:

10624

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0352

AC:

2396

AN:

68020

Other (OTH)

AF:

0.0444

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

307

614

922

1229

1536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0362

Hom.:

233

Bravo

AF:

0.0451

Asia WGS

AF:

0.0830

AC:

288

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.62

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over