9-94606867-C-T

Position:

chr9-94606867-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000375326.9(FBP1):c.653G>A(p.Arg218Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 1,613,876 control chromosomes in the GnomAD database, including 713,898 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70164 hom., cov: 33)

Exomes 𝑓: 0.94 ( 643734 hom. )

Consequence

FBP1
ENST00000375326.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.154

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.689069E-7).

BP6

Variant 9-94606867-C-T is Benign according to our data. Variant chr9-94606867-C-T is described in ClinVar as [Benign]. Clinvar id is 256323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-94606867-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBP1	NM_000507.4 linkuse as main transcript	c.653G>A	p.Arg218Lys	missense_variant	5/7	ENST00000375326.9	NP_000498.2	P09467
FBP1	NM_001127628.2 linkuse as main transcript	c.653G>A	p.Arg218Lys	missense_variant	6/8		NP_001121100.1	P09467Q2TU34
FBP1	XM_006717005.5 linkuse as main transcript	c.407G>A	p.Arg136Lys	missense_variant	5/7		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9 linkuse as main transcript	c.653G>A	p.Arg218Lys	missense_variant	5/7	1	NM_000507.4	ENSP00000364475.5		P09467

Frequencies

GnomAD3 genomes

AF:

0.960

AC:

146064

AN:

152202

Hom.:

70103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.987

Gnomad AMI

AF:

0.956

Gnomad AMR

AF:

0.973

Gnomad ASJ

AF:

0.964

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.960

Gnomad FIN

AF:

0.943

Gnomad MID

AF:

0.972

Gnomad NFE

AF:

0.939

Gnomad OTH

AF:

0.961

GnomAD3 exomes

AF:

0.956

AC:

240380

AN:

251358

Hom.:

115021

AF XY:

0.955

AC XY:

129666

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.986

Gnomad AMR exome

AF:

0.980

Gnomad ASJ exome

AF:

0.962

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.954

Gnomad FIN exome

AF:

0.945

Gnomad NFE exome

AF:

0.940

Gnomad OTH exome

AF:

0.953

GnomAD4 exome

AF:

0.938

AC:

1371406

AN:

1461556

Hom.:

643734

Cov.:

AF XY:

0.939

AC XY:

682622

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.987

Gnomad4 AMR exome

AF:

0.978

Gnomad4 ASJ exome

AF:

0.959

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.953

Gnomad4 FIN exome

AF:

0.945

Gnomad4 NFE exome

AF:

0.931

Gnomad4 OTH exome

AF:

0.945

GnomAD4 genome

AF:

0.960

AC:

146184

AN:

152320

Hom.:

70164

Cov.:

AF XY:

0.960

AC XY:

71501

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.987

Gnomad4 AMR

AF:

0.973

Gnomad4 ASJ

AF:

0.964

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.960

Gnomad4 FIN

AF:

0.943

Gnomad4 NFE

AF:

0.939

Gnomad4 OTH

AF:

0.961

Alfa

AF:

0.944

Hom.:

167184

Bravo

AF:

0.962

TwinsUK

AF:

0.927

AC:

3436

ALSPAC

AF:

0.926

AC:

3567

ESP6500AA

AF:

0.983

AC:

4330

ESP6500EA

AF:

0.940

AC:

8083

ExAC

AF:

0.956

AC:

116075

Asia WGS

AF:

0.977

AC:

3393

AN:

3478

EpiCase

AF:

0.939

EpiControl

AF:

0.938

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Fructose-biphosphatase deficiency

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.10

.;T;T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.32

T;.;T;T

MetaRNN

Benign

5.7e-7

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.16

.;N;N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.81

.;N;N;N

REVEL

Benign

0.083

Sift

Benign

1.0

.;T;T;T

Sift4G

Benign

1.0

.;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.026

MPC

0.30

ClinPred

0.0052

GERP RS

1.6

Varity_R

0.29

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over