rs145771944

Positions:

chr9-94603533-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_000507.4(FBP1):c.865A>T(p.Met289Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000631 in 1,614,152 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

FBP1
NM_000507.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.96

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:

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

PCAT7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01455909).

BP6

Variant 9-94603533-T-A is Benign according to our data. Variant chr9-94603533-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 214360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00344 (524/152262) while in subpopulation AFR AF= 0.012 (498/41552). AF 95% confidence interval is 0.0111. There are 0 homozygotes in gnomad4. There are 224 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FBP1	NM_000507.4 linkuse as main transcript	c.865A>T	p.Met289Leu	missense_variant	7/7	ENST00000375326.9
FBP1	NM_001127628.2 linkuse as main transcript	c.865A>T	p.Met289Leu	missense_variant	8/8
FBP1	XM_006717005.5 linkuse as main transcript	c.619A>T	p.Met207Leu	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBP1	ENST00000375326.9 linkuse as main transcript	c.865A>T	p.Met289Leu	missense_variant	7/7	1	NM_000507.4	P1
PCAT7	ENST00000647389.1 linkuse as main transcript	n.1885T>A		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

524

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.000923

AC:

232

AN:

251486

Hom.:

AF XY:

0.000765

AC XY:

104

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000338

AC:

494

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

218

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0123

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.00344

AC:

524

AN:

152262

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

224

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000581

Hom.:

Bravo

AF:

0.00405

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00124

AC:

151

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 22, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 26, 2015

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. -

FBP1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 27, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Fructose-biphosphatase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.15

.;T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

D;.;D

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.6

.;L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.46

.;N;N

REVEL

Benign

0.077

Sift

Benign

0.15

.;T;T

Sift4G

Benign

0.18

.;T;T

Polyphen

0.0010

.;B;B

Vest4

0.24, 0.24

MutPred

0.42

.;Loss of ubiquitination at K291 (P = 0.092);Loss of ubiquitination at K291 (P = 0.092);

MVP

0.71

MPC

0.28

ClinPred

0.013

GERP RS

4.1

Varity_R

0.39

gMVP

0.46

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