Variant 9-94559122-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP4_StrongBP6_ModerateBS2

The NM_003837.4(FBP2):c.836T>C(p.Leu279Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00895 in 1,611,416 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 82 hom. )

Consequence

FBP2
NM_003837.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.72

Variant links:

Genes affected

FBP2 (HGNC:3607): (fructose-bisphosphatase 2) This gene encodes a gluconeogenesis regulatory enzyme which catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. [provided by RefSeq, Jul 2008]

FBP2 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 -9 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_noAF, Cadd, Eigen, M_CAP, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.038577616).

BP6

Variant 9-94559122-A-G is Benign according to our data. Variant chr9-94559122-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3257644.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 754 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBP2	NM_003837.4 linkuse as main transcript	c.836T>C	p.Leu279Pro	missense_variant	7/7	ENST00000375337.4
PCAT7	NR_121566.2 linkuse as main transcript	n.540A>G		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FBP2	ENST00000375337.4 linkuse as main transcript	c.836T>C	p.Leu279Pro	missense_variant	7/7	1	NM_003837.4	P1
PCAT7	ENST00000647389.1 linkuse as main transcript	n.411A>G		non_coding_transcript_exon_variant	2/9
PCAT7	ENST00000452148.3 linkuse as main transcript	n.411A>G		non_coding_transcript_exon_variant	2/3	2
PCAT7	ENST00000644721.1 linkuse as main transcript	n.417A>G		non_coding_transcript_exon_variant	2/3

Frequencies

GnomAD3 genomes

AF:

0.00495

AC:

754

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00955

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00497

AC:

1245

AN:

250702

Hom.:

AF XY:

0.00486

AC XY:

658

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.000841

Gnomad ASJ exome

AF:

0.000399

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00167

Gnomad NFE exome

AF:

0.00983

Gnomad OTH exome

AF:

0.00507

GnomAD4 exome

AF:

0.00936

AC:

13662

AN:

1459110

Hom.:

Cov.:

AF XY:

0.00901

AC XY:

6538

AN XY:

725456

show subpopulations

Gnomad4 AFR exome

AF:

0.00141

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00294

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.00646

GnomAD4 genome

AF:

0.00495

AC:

754

AN:

152306

Hom.:

Cov.:

AF XY:

0.00423

AC XY:

315

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00956

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00832

Hom.:

Bravo

AF:

0.00500

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0117

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.00497

AC:

603

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00812

EpiControl

AF:

0.00895

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

FBP2: BS2; PCAT7: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.41

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.039

MetaSVM

Uncertain

0.58

MutationAssessor

Pathogenic

4.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-6.2

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.97

MVP

0.95

MPC

0.72

ClinPred

0.15

GERP RS

4.3

Varity_R

0.94

gMVP

0.96

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