rs2297084

Positions:

• chr9-94606801-G-A
• chr9-94606801-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000507.4(FBP1):​c.705+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,610,456 control chromosomes in the GnomAD database, including 206,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (19869 hom., cov: 33)
  • Exomes 𝑓: 0.50 (187083 hom.)
• Consequence: FBP1 NM_000507.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.879

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-94606801-G-A is Benign according to our data. Variant chr9-94606801-G-A is described in ClinVar as [Benign]. Clinvar id is 256324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-94606801-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBP1	NM_000507.4	c.705+14C>T		intron_variant		ENST00000375326.9	NP_000498.2
FBP1	NM_001127628.2	c.705+14C>T		intron_variant			NP_001121100.1
FBP1	XM_006717005.5	c.459+14C>T		intron_variant			XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9	c.705+14C>T		intron_variant		1	NM_000507.4	ENSP00000364475.5

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77319 AN: 151950 Hom.: 19854 Cov.: 33

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.537

GnomAD3 exomes AF: 0.517 AC: 127174 AN: 246200 Hom.: 33936 AF XY: 0.511 AC XY: 68031 AN XY: 133212

Gnomad AFR exome AF: 0.475

Gnomad AMR exome AF: 0.698

Gnomad ASJ exome AF: 0.659

Gnomad EAS exome AF: 0.398

Gnomad SAS exome AF: 0.427

Gnomad FIN exome AF: 0.430

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.528

GnomAD4 exome AF: 0.503 AC: 733738 AN: 1458388 Hom.: 187083 Cov.: 39 AF XY: 0.501 AC XY: 363778 AN XY: 725448

Gnomad4 AFR exome AF: 0.483

Gnomad4 AMR exome AF: 0.696

Gnomad4 ASJ exome AF: 0.658

Gnomad4 EAS exome AF: 0.391

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.509 AC: 77376 AN: 152068 Hom.: 19869 Cov.: 33 AF XY: 0.506 AC XY: 37575 AN XY: 74324

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.536

Alfa AF: 0.541 Hom.: 4153

Bravo AF: 0.525

Asia WGS AF: 0.433 AC: 1506 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fructose-biphosphatase deficiency Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -

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	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.052
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs2297084; hg19: chr9-97369083; COSMIC: COSV64688692; COSMIC: COSV64688692;