Genetic Variant FBH1:c.753+43C>T (chr10-5906675-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

Publications

5 publications found

Variant links:

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]

FBH1 links:

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ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FBH1	NM_178150.3	MANE Select	c.753+43C>T	intron	N/A	NP_835363.1	Q8NFZ0-1
FBH1	NM_032807.5		c.906+43C>T	intron	N/A	NP_116196.3
FBH1	NM_001258452.2		c.531+43C>T	intron	N/A	NP_001245381.1	F6UZG9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FBH1	ENST00000362091.9	TSL:1 MANE Select	c.753+43C>T	intron	N/A	ENSP00000355415.4	Q8NFZ0-1
FBH1	ENST00000379999.6	TSL:1	c.906+43C>T	intron	N/A	ENSP00000369335.5	Q8NFZ0-2
FBH1	ENST00000908866.1		c.753+43C>T	intron	N/A	ENSP00000578925.1

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44052

AN:

151934

Hom.:

6954

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.303

AC XY:

201631

AN XY:

664510

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

14090

28179

42269

56358

70448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10670

21340

32010

42680

53350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.290

AC:

44063

AN:

152052

Hom.:

6953

Cov.:

AF XY:

0.284

AC XY:

21137

AN XY:

74316

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.346

AC:

23521

AN:

67964

Other (OTH)

AF:

0.314

AC:

663

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1576

3151

4727

6302

7878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.029

(source)

DANN

Benign

0.51

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over