rs2274030

chr10-5924229-A-Gchr10-5924229-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178150.3(FBH1):c.2399-82A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,394,136 control chromosomes in the GnomAD database, including 517,017 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 0.86 (55698 hom., cov: 31)
  • Exomes 𝑓: 0.86 (461319 hom.)
• Consequence: FBH1 NM_178150.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345

Genes affected

FBH1 (HGNC:13620): (F-box DNA helicase 1) This gene encodes a member of the F-box protein family, members of which are characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into three 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 Fbx class. It contains an F-box motif and seven conserved helicase motifs, and has both DNA-dependent ATPase and DNA unwinding activities. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBH1	NM_178150.3	c.2399-82A>G		intron_variant		ENST00000362091.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBH1	ENST00000362091.9	c.2399-82A>G		intron_variant		1	NM_178150.3	P1

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129938 AN: 151948 Hom.: 55640 Cov.: 31

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.842

GnomAD4 exome AF: 0.861 AC: 1069274 AN: 1242070 Hom.: 461319 Cov.: 16 AF XY: 0.857 AC XY: 535831 AN XY: 625496

Gnomad4 AFR exome AF: 0.841

Gnomad4 AMR exome AF: 0.915

Gnomad4 ASJ exome AF: 0.780

Gnomad4 EAS exome AF: 0.864

Gnomad4 SAS exome AF: 0.759

Gnomad4 FIN exome AF: 0.894

Gnomad4 NFE exome AF: 0.869

Gnomad4 OTH exome AF: 0.851

GnomAD4 genome AF: 0.855 AC: 130058 AN: 152066 Hom.: 55698 Cov.: 31 AF XY: 0.854 AC XY: 63504 AN XY: 74336

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.859

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.866

Gnomad4 OTH AF: 0.843

Alfa AF: 0.867 Hom.: 7348

Bravo AF: 0.856

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.37
Dann	Benign	0.25

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: rs2274030; hg19: chr10-5966192;