rs16910744

Positions:

• chr9-94620386-C-A
• chr9-94620386-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BA1

The NM_000507.4(FBP1):​c.276G>T​(p.Thr92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00944 in 1,614,140 control chromosomes in the GnomAD database, including 1,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (551 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (519 hom.)
• Consequence: FBP1 NM_000507.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.141

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BP6: Variant 9-94620386-C-A is Benign according to our data. Variant chr9-94620386-C-A is described in ClinVar as [Benign]. Clinvar id is 137364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.141 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBP1	NM_000507.4	c.276G>T	p.Thr92=	synonymous_variant	2/7	ENST00000375326.9	NP_000498.2
FBP1	NM_001127628.2	c.276G>T	p.Thr92=	synonymous_variant	3/8		NP_001121100.1
FBP1	XM_006717005.5	c.30G>T	p.Thr10=	synonymous_variant	2/7		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9	c.276G>T	p.Thr92=	synonymous_variant	2/7	1	NM_000507.4	ENSP00000364475	P1

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7039 AN: 152144 Hom.: 544 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0315

GnomAD3 exomes AF: 0.0132 AC: 3330 AN: 251484 Hom.: 248 AF XY: 0.00981 AC XY: 1334 AN XY: 135922

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.0109

Gnomad ASJ exome AF: 0.00565

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00134

Gnomad OTH exome AF: 0.00879

GnomAD4 exome AF: 0.00559 AC: 8166 AN: 1461878 Hom.: 519 Cov.: 32 AF XY: 0.00491 AC XY: 3571 AN XY: 727238

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.00478

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000406

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00104

Gnomad4 OTH exome AF: 0.0124

GnomAD4 genome AF: 0.0465 AC: 7077 AN: 152262 Hom.: 551 Cov.: 32 AF XY: 0.0439 AC XY: 3268 AN XY: 74454

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00116

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0212 Hom.: 120

Bravo AF: 0.0532

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.00142

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 27, 2012	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Fructose-biphosphatase deficiency Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
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:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	5.4
DANN	Benign	0.65

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: rs16910744; hg19: chr9-97382668;