Genetic Variant FBP2:p.Leu279Pro (chr9-94559122-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PP3BP4_StrongBP6_ModerateBS2

The NM_003837.4(FBP2):c.836T>C(p.Leu279Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00895 in 1,611,416 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 82 hom. )

Consequence

FBP2
NM_003837.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.72

Publications

7 publications found

Variant links:

Genes affected

FBP2 (HGNC:3607): (fructose-bisphosphatase 2) This gene encodes a gluconeogenesis regulatory enzyme which catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. [provided by RefSeq, Jul 2008]

FBP2 links:

PCAT7 (HGNC:48824): (prostate cancer associated transcript 7)

PCAT7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 10: AlphaMissense, BayesDel_noAF, Cadd, Eigen, M_CAP, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.038577616).

BP6

Variant 9-94559122-A-G is Benign according to our data. Variant chr9-94559122-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3257644.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 754 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBP2	NM_003837.4 link	c.836T>C	p.Leu279Pro	missense_variant	Exon 7 of 7	ENST00000375337.4	NP_003828.2	O00757

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBP2	ENST00000375337.4 link	c.836T>C	p.Leu279Pro	missense_variant	Exon 7 of 7	1	NM_003837.4	ENSP00000364486.3		O00757

Frequencies

GnomAD3 genomes

AF:

0.00495

AC:

754

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00955

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00497

AC:

1245

AN:

250702

AF XY:

0.00486

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.000841

Gnomad ASJ exome

AF:

0.000399

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00167

Gnomad NFE exome

AF:

0.00983

Gnomad OTH exome

AF:

0.00507

GnomAD4 exome

AF:

0.00936

AC:

13662

AN:

1459110

Hom.:

Cov.:

AF XY:

0.00901

AC XY:

6538

AN XY:

725456

show subpopulations

African (AFR)

AF:

0.00141

AC:

AN:

33418

American (AMR)

AF:

0.00103

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

86124

European-Finnish (FIN)

AF:

0.00294

AC:

157

AN:

53386

Middle Eastern (MID)

AF:

0.000399

AC:

AN:

5016

European-Non Finnish (NFE)

AF:

0.0117

AC:

13011

AN:

1110530

Other (OTH)

AF:

0.00646

AC:

389

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

636

1272

1908

2544

3180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00495

AC:

754

AN:

152306

Hom.:

Cov.:

AF XY:

0.00423

AC XY:

315

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

41574

American (AMR)

AF:

0.00124

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00956

AC:

650

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

121

161

201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00792

Hom.:

Bravo

AF:

0.00500

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0117

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.00497

AC:

603

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00812

EpiControl

AF:

0.00895

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FBP2: BS2; PCAT7: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.41

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.039

MetaSVM

Uncertain

0.58

MutationAssessor

Pathogenic

4.4

PhyloP100

8.7

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-6.2

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.97

MVP

0.95

MPC

0.72

ClinPred

0.15

GERP RS

4.3

Varity_R

0.94

gMVP

0.96

Mutation Taster

=60/40

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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9-94559122-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over