NM_000507.4:c.426+7C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000507.4(FBP1):c.426+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,590,510 control chromosomes in the GnomAD database, including 95,582 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 7989 hom., cov: 32)

Exomes 𝑓: 0.34 ( 87593 hom. )

Consequence

FBP1
NM_000507.4 splice_region, intron

Scores

Splicing: ADA: 0.0003523

Clinical Significance

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

Conservation

PhyloP100: 0.387

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 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 (BayesDel_noAF=-0.79).

BP6

Variant 9-94617761-G-A is Benign according to our data. Variant chr9-94617761-G-A is described in ClinVar as [Benign]. Clinvar id is 256320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-94617761-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FBP1	NM_000507.4 link	c.426+7C>T	splice_region_variant, intron_variant	Intron 3 of 6	ENST00000375326.9	NP_000498.2	P09467
FBP1	NM_001127628.2 link	c.426+7C>T	splice_region_variant, intron_variant	Intron 4 of 7		NP_001121100.1	P09467Q2TU34
FBP1	XM_006717005.5 link	c.180+7C>T	splice_region_variant, intron_variant	Intron 3 of 6		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9 link	c.426+7C>T		splice_region_variant, intron_variant	Intron 3 of 6	1	NM_000507.4	ENSP00000364475.5		P09467

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48755

AN:

151770

Hom.:

7978

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.555

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.302

GnomAD2 exomes

AF:

0.336

AC:

84275

AN:

250660

AF XY:

0.341

show subpopulations

Gnomad AFR exome

AF:

0.280

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.551

Gnomad FIN exome

AF:

0.386

Gnomad NFE exome

AF:

0.338

Gnomad OTH exome

AF:

0.324

GnomAD4 exome

AF:

0.343

AC:

492730

AN:

1438622

Hom.:

87593

Cov.:

AF XY:

0.344

AC XY:

246727

AN XY:

717162

show subpopulations

African (AFR)

AF:

0.272

AC:

8981

AN:

33062

American (AMR)

AF:

0.195

AC:

8697

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

6257

AN:

26032

East Asian (EAS)

AF:

0.585

AC:

23140

AN:

39536

South Asian (SAS)

AF:

0.383

AC:

32886

AN:

85754

European-Finnish (FIN)

AF:

0.399

AC:

21231

AN:

53236

Middle Eastern (MID)

AF:

0.241

AC:

1380

AN:

5724

European-Non Finnish (NFE)

AF:

0.340

AC:

370543

AN:

1090986

Other (OTH)

AF:

0.329

AC:

19615

AN:

59626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

14151

28303

42454

56606

70757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.321

AC:

48804

AN:

151888

Hom.:

7989

Cov.:

AF XY:

0.322

AC XY:

23877

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.285

AC:

11787

AN:

41404

American (AMR)

AF:

0.234

AC:

3565

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

805

AN:

3470

East Asian (EAS)

AF:

0.554

AC:

2858

AN:

5158

South Asian (SAS)

AF:

0.392

AC:

1880

AN:

4800

European-Finnish (FIN)

AF:

0.389

AC:

4096

AN:

10526

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.336

AC:

22867

AN:

67968

Other (OTH)

AF:

0.306

AC:

644

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1689

3377

5066

6754

8443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.317

Hom.:

12526

Bravo

AF:

0.306

Asia WGS

AF:

0.422

AC:

1465

AN:

3478

EpiCase

AF:

0.329

EpiControl

AF:

0.328

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

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

-0.79

CADD

Benign

2.5

(source)

DANN

Benign

0.41

PhyloP100

0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00035

dbscSNV1_RF

Benign

0.028

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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NM_000507.4:c.426+7C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over