9-94606823-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000507.4(FBP1):c.697T>A(p.Phe233Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,613,752 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F233L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0018 ( 6 hom., cov: 34)

Exomes 𝑓: 0.0016 ( 56 hom. )

Consequence

FBP1
NM_000507.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 9.32

Publications

7 publications found

Variant links:

Genes affected

FBP1 (HGNC:3606): (fructose-bisphosphatase 1) Fructose-1,6-bisphosphatase 1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. Fructose-1,6-diphosphatase deficiency is associated with hypoglycemia and metabolic acidosis. [provided by RefSeq, Jul 2008]

FBP1 Gene-Disease associations (from GenCC):

fructose-1,6-bisphosphatase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp, Orphanet

FBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008790016).

BP6

Variant 9-94606823-A-T is Benign according to our data. Variant chr9-94606823-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0018 (274/152302) while in subpopulation EAS AF = 0.047 (244/5188). AF 95% confidence interval is 0.0422. There are 6 homozygotes in GnomAd4. There are 146 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000507.4. 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
	FBP1	NM_000507.4	MANE Select	c.697T>A	p.Phe233Ile	missense	Exon 5 of 7	NP_000498.2
	FBP1	NM_001127628.2		c.697T>A	p.Phe233Ile	missense	Exon 6 of 8	NP_001121100.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FBP1	ENST00000375326.9	TSL:1 MANE Select	c.697T>A	p.Phe233Ile	missense	Exon 5 of 7	ENSP00000364475.5
FBP1	ENST00000884868.1		c.697T>A	p.Phe233Ile	missense	Exon 6 of 8	ENSP00000554927.1
FBP1	ENST00000945615.1		c.697T>A	p.Phe233Ile	missense	Exon 5 of 7	ENSP00000615674.1

Frequencies

GnomAD3 genomes

AF:

0.00181

AC:

275

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0471

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00345

AC:

864

AN:

250792

AF XY:

0.00305

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0434

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00159

AC:

2325

AN:

1461450

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1121

AN XY:

727028

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33464

American (AMR)

AF:

0.0000895

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0505

AC:

2003

AN:

39696

South Asian (SAS)

AF:

0.00125

AC:

108

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000703

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0000558

AC:

AN:

1111766

Other (OTH)

AF:

0.00220

AC:

133

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

118

237

355

474

592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00180

AC:

274

AN:

152302

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

146

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41574

American (AMR)

AF:

0.0000654

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0470

AC:

244

AN:

5188

South Asian (SAS)

AF:

0.00145

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68014

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000131

Hom.:

Bravo

AF:

0.00182

ExAC

AF:

0.00334

AC:

405

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Fructose-biphosphatase deficiency (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0088

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.7

PhyloP100

9.3

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.33

Sift

Benign

0.085

Sift4G

Benign

0.36

Polyphen

0.42

Vest4

0.47

MVP

0.77

MPC

0.56

ClinPred

0.057

GERP RS

5.5

Varity_R

0.60

gMVP

0.82

Mutation Taster

=80/20

polymorphism

(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