dbSNP rs7830622: FBXO32: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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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