rs2294088

Variant names:

• chr8-123514367-G-A
• rs2294088
• NM_058229.4:c.373-34C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-123514367-G-A
• chr8-123514367-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_058229.4(FBXO32):​c.373-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,558,972 control chromosomes in the GnomAD database, including 75,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10601 hom., cov: 32)
  • Exomes 𝑓: 0.29 (64934 hom.)
• Consequence: FBXO32 NM_058229.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.805
• Publications: 18 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 8-123514367-G-A is Benign according to our data. Variant chr8-123514367-G-A is described in ClinVar as Benign. ClinVar VariationId is 1269899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO32	NM_058229.4	c.373-34C>T		intron_variant	Intron 4 of 8	ENST00000517956.5	NP_478136.1
FBXO32	NM_001242463.2	c.373-7793C>T		intron_variant	Intron 4 of 6		NP_001229392.1
FBXO32	NM_148177.3	c.-63-34C>T		intron_variant	Intron 1 of 5		NP_680482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO32	ENST00000517956.5	c.373-34C>T		intron_variant	Intron 4 of 8	1	NM_058229.4	ENSP00000428205.1
FBXO32	ENST00000443022.2	c.373-7793C>T		intron_variant	Intron 4 of 6	1		ENSP00000390790.2
FBXO32	ENST00000287396.2	n.247-34C>T		intron_variant	Intron 1 of 5	1
FBXO32	ENST00000521719.5	n.548-34C>T		intron_variant	Intron 4 of 5	3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54024 AN: 151900 Hom.: 10584 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.338

GnomAD2 exomes AF: 0.353 AC: 78380 AN: 221754 AF XY: 0.335

Gnomad AFR exome AF: 0.469

Gnomad AMR exome AF: 0.528

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.675

Gnomad FIN exome AF: 0.349

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.292 AC: 411162 AN: 1406954 Hom.: 64934 Cov.: 21 AF XY: 0.289 AC XY: 202454 AN XY: 700892

African (AFR) AF: 0.468 AC: 14971 AN: 31960

American (AMR) AF: 0.512 AC: 21415 AN: 41830

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5170 AN: 25380

East Asian (EAS) AF: 0.639 AC: 24665 AN: 38626

South Asian (SAS) AF: 0.229 AC: 18653 AN: 81370

European-Finnish (FIN) AF: 0.345 AC: 18143 AN: 52558

Middle Eastern (MID) AF: 0.217 AC: 1227 AN: 5660

European-Non Finnish (NFE) AF: 0.270 AC: 289371 AN: 1071180

Other (OTH) AF: 0.301 AC: 17547 AN: 58390

GnomAD4 genome AF: 0.356 AC: 54086 AN: 152018 Hom.: 10601 Cov.: 32 AF XY: 0.360 AC XY: 26785 AN XY: 74326

African (AFR) AF: 0.464 AC: 19239 AN: 41450

American (AMR) AF: 0.431 AC: 6580 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 685 AN: 3472

East Asian (EAS) AF: 0.656 AC: 3389 AN: 5170

South Asian (SAS) AF: 0.224 AC: 1079 AN: 4814

European-Finnish (FIN) AF: 0.362 AC: 3823 AN: 10574

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18284 AN: 67962

Other (OTH) AF: 0.338 AC: 712 AN: 2108

Alfa AF: 0.301 Hom.: 27672

Bravo AF: 0.370

Asia WGS AF: 0.425 AC: 1475 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2294088; hg19: chr8-124526607; COSMIC: COSV54892967;