10-5924229-A-G

Variant names:

• chr10-5924229-A-G
• rs2274030
• NM_178150.3:c.2399-82A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178150.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBH1	NM_178150.3	MANE Select	c.2399-82A>G		intron	N/A	NP_835363.1	Q8NFZ0-1
	FBH1	NM_032807.5		c.2552-82A>G		intron	N/A	NP_116196.3
	FBH1	NM_001258452.2		c.2177-82A>G		intron	N/A	NP_001245381.1	F6UZG9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBH1	ENST00000362091.9	TSL:1 MANE Select	c.2399-82A>G		intron	N/A	ENSP00000355415.4	Q8NFZ0-1
	FBH1	ENST00000379999.6	TSL:1	c.2552-82A>G		intron	N/A	ENSP00000369335.5	Q8NFZ0-2
	FBH1	ENST00000908866.1		c.2399-82A>G		intron	N/A	ENSP00000578925.1

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

African (AFR) AF: 0.841 AC: 24128 AN: 28674

American (AMR) AF: 0.915 AC: 36527 AN: 39938

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 18788 AN: 24102

East Asian (EAS) AF: 0.864 AC: 32485 AN: 37618

South Asian (SAS) AF: 0.759 AC: 59829 AN: 78812

European-Finnish (FIN) AF: 0.894 AC: 42720 AN: 47770

Middle Eastern (MID) AF: 0.796 AC: 3638 AN: 4568

European-Non Finnish (NFE) AF: 0.869 AC: 806231 AN: 927812

Other (OTH) AF: 0.851 AC: 44928 AN: 52776

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

African (AFR) AF: 0.839 AC: 34741 AN: 41426

American (AMR) AF: 0.884 AC: 13506 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2695 AN: 3472

East Asian (EAS) AF: 0.859 AC: 4432 AN: 5158

South Asian (SAS) AF: 0.752 AC: 3626 AN: 4822

European-Finnish (FIN) AF: 0.893 AC: 9455 AN: 10590

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.866 AC: 58916 AN: 68008

Other (OTH) AF: 0.843 AC: 1774 AN: 2104

Alfa AF: 0.864 Hom.: 74205

Bravo AF: 0.856

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.25
PhyloP100		-0.34
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: rs2274030; hg19: chr10-5966192;