rs1042144

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000507.4(FBP1):c.651C>T(p.Ala217Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,613,350 control chromosomes in the GnomAD database, including 93,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7599 hom., cov: 32)

Exomes 𝑓: 0.34 ( 86106 hom. )

Consequence

FBP1
NM_000507.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.19

Publications

22 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 9-94606869-G-A is Benign according to our data. Variant chr9-94606869-G-A is described in ClinVar as Benign. ClinVar VariationId is 256322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBP1	NM_000507.4 link	c.651C>T	p.Ala217Ala	synonymous_variant	Exon 5 of 7	ENST00000375326.9	NP_000498.2	P09467
FBP1	NM_001127628.2 link	c.651C>T	p.Ala217Ala	synonymous_variant	Exon 6 of 8		NP_001121100.1	P09467Q2TU34
FBP1	XM_006717005.5 link	c.405C>T	p.Ala135Ala	synonymous_variant	Exon 5 of 7		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9 link	c.651C>T	p.Ala217Ala	synonymous_variant	Exon 5 of 7	1	NM_000507.4	ENSP00000364475.5		P09467

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

47624

AN:

152056

Hom.:

7592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.293

GnomAD2 exomes

AF:

0.329

AC:

82659

AN:

251338

AF XY:

0.333

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.226

Gnomad EAS exome

AF:

0.549

Gnomad FIN exome

AF:

0.377

Gnomad NFE exome

AF:

0.333

Gnomad OTH exome

AF:

0.316

GnomAD4 exome

AF:

0.338

AC:

493510

AN:

1461176

Hom.:

86106

Cov.:

AF XY:

0.339

AC XY:

246236

AN XY:

726936

show subpopulations

African (AFR)

AF:

0.264

AC:

8821

AN:

33466

American (AMR)

AF:

0.190

AC:

8501

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

5910

AN:

26126

East Asian (EAS)

AF:

0.558

AC:

22149

AN:

39696

South Asian (SAS)

AF:

0.368

AC:

31741

AN:

86236

European-Finnish (FIN)

AF:

0.388

AC:

20736

AN:

53412

Middle Eastern (MID)

AF:

0.222

AC:

1276

AN:

5750

European-Non Finnish (NFE)

AF:

0.337

AC:

374853

AN:

1111410

Other (OTH)

AF:

0.323

AC:

19523

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

17360

34720

52079

69439

86799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12196

24392

36588

48784

60980

<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:

0.313

AC:

47671

AN:

152174

Hom.:

7599

Cov.:

AF XY:

0.313

AC XY:

23273

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.272

AC:

11296

AN:

41542

American (AMR)

AF:

0.230

AC:

3518

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

761

AN:

3466

East Asian (EAS)

AF:

0.541

AC:

2789

AN:

5156

South Asian (SAS)

AF:

0.377

AC:

1817

AN:

4820

European-Finnish (FIN)

AF:

0.378

AC:

4001

AN:

10578

Middle Eastern (MID)

AF:

0.264

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.332

AC:

22562

AN:

67996

Other (OTH)

AF:

0.297

AC:

629

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1666

3332

4999

6665

8331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.319

Hom.:

5819

Bravo

AF:

0.300

Asia WGS

AF:

0.421

AC:

1461

AN:

3478

EpiCase

AF:

0.323

EpiControl

AF:

0.320

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Aug 30, 2012

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Fructose-biphosphatase deficiency

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

2.2

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over