chr9-94606823-A-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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=0.008790016).

BP6

Variant 9-94606823-A-T is Benign according to our data. Variant chr9-94606823-A-T is described in ClinVar as [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBP1	NM_000507.4 link	c.697T>A	p.Phe233Ile	missense_variant	Exon 5 of 7	ENST00000375326.9	NP_000498.2	P09467
FBP1	NM_001127628.2 link	c.697T>A	p.Phe233Ile	missense_variant	Exon 6 of 8		NP_001121100.1	P09467Q2TU34
FBP1	XM_006717005.5 link	c.451T>A	p.Phe151Ile	missense_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.697T>A	p.Phe233Ile	missense_variant	Exon 5 of 7	1	NM_000507.4	ENSP00000364475.5		P09467

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

GnomAD3 exomes

AF:

0.00345

AC:

864

AN:

250792

Hom.:

AF XY:

0.00305

AC XY:

414

AN XY:

135566

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 SAS exome

AF:

0.00118

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

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0505

Gnomad4 SAS exome

AF:

0.00125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000558

Gnomad4 OTH exome

AF:

0.00220

GnomAD4 genome

AF:

0.00180

AC:

274

AN:

152302

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

146

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0470

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.00182

ExAC

AF:

0.00334

AC:

405

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fructose-biphosphatase deficiency

Benign:2

Jan 23, 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: Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not specified

Benign:1

May 16, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

.;D;D;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;.;D;T

MetaRNN

Benign

0.0088

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.7

.;M;M;.

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.5

.;D;D;D

REVEL

Uncertain

0.33

Sift

Benign

0.085

.;T;T;T

Sift4G

Benign

0.36

.;T;T;T

Polyphen

0.42

.;B;B;.

Vest4

0.47

MVP

0.77

MPC

0.56

ClinPred

0.057

GERP RS

5.5

Varity_R

0.60

gMVP

0.82

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

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