10-5906675-C-T

Variant names:

• chr10-5906675-C-T
• rs7082434
• NM_178150.3:c.753+43C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178150.3(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 NM_178150.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 5 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=-0.85).
• 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 rank	MANE	Protein	UniProt
FBH1	NM_178150.3	c.753+43C>T		intron_variant	Intron 3 of 20	ENST00000362091.9	NP_835363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBH1	ENST00000362091.9	c.753+43C>T		intron_variant	Intron 3 of 20	1	NM_178150.3	ENSP00000355415.4

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

GnomAD2 exomes AF: 0.263 AC: 52764 AN: 200876 AF XY: 0.266

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 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

African (AFR) AF: 0.244 AC: 7431 AN: 30450

American (AMR) AF: 0.181 AC: 6982 AN: 38542

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 5969 AN: 22628

East Asian (EAS) AF: 0.0142 AC: 552 AN: 38870

South Asian (SAS) AF: 0.150 AC: 11754 AN: 78192

European-Finnish (FIN) AF: 0.335 AC: 12990 AN: 38728

Middle Eastern (MID) AF: 0.356 AC: 1917 AN: 5384

European-Non Finnish (NFE) AF: 0.337 AC: 346518 AN: 1029730

Other (OTH) AF: 0.294 AC: 16469 AN: 56080

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

African (AFR) AF: 0.252 AC: 10431 AN: 41456

American (AMR) AF: 0.255 AC: 3893 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3470

East Asian (EAS) AF: 0.0232 AC: 120 AN: 5166

South Asian (SAS) AF: 0.144 AC: 694 AN: 4828

European-Finnish (FIN) AF: 0.336 AC: 3550 AN: 10570

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23521 AN: 67964

Other (OTH) AF: 0.314 AC: 663 AN: 2114

Alfa AF: 0.308 Hom.: 3043

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
PhyloP100		-1.2
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: rs7082434; hg19: chr10-5948638;