rs7082434

Positions:

• chr10-5906675-C-T

Variant summary

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

The ENST00000362091.9(FBH1):​c.753+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,490,656 control chromosomes in the GnomAD database, including 74,201 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 0.29 (6953 hom., cov: 32)
  • Exomes 𝑓: 0.31 (67248 hom.)
• Consequence: FBH1 ENST00000362091.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBH1	NM_178150.3	c.753+43C>T		intron_variant		ENST00000362091.9	NP_835363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBH1	ENST00000362091.9	c.753+43C>T		intron_variant		1	NM_178150.3	ENSP00000355415	P1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44052 AN: 151934 Hom.: 6954 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.316

GnomAD3 exomes AF: 0.263 AC: 52764 AN: 200876 Hom.: 8093 AF XY: 0.266 AC XY: 29125 AN XY: 109564

Gnomad AFR exome AF: 0.251

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.267

Gnomad EAS exome AF: 0.0231

Gnomad SAS exome AF: 0.155

Gnomad FIN exome AF: 0.338

Gnomad NFE exome AF: 0.349

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.307 AC: 410582 AN: 1338604 Hom.: 67248 Cov.: 20 AF XY: 0.303 AC XY: 201631 AN XY: 664510

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.181

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.0142

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.290 AC: 44063 AN: 152052 Hom.: 6953 Cov.: 32 AF XY: 0.284 AC XY: 21137 AN XY: 74316

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.0232

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.314

Alfa AF: 0.323 Hom.: 1845

Bravo AF: 0.283

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.029
DANN	Benign	0.51

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: rs7082434; hg19: chr10-5948638;