rs1042144

Positions:

• chr9-94606869-G-A
• chr9-94606869-G-C
• chr9-94606869-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000507.4(FBP1):​c.651C>T​(p.Ala217=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,613,350 control chromosomes in the GnomAD database, including 93,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7599 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86106 hom.)
• Consequence: FBP1 NM_000507.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.19

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 9-94606869-G-A is Benign according to our data. Variant chr9-94606869-G-A is described in ClinVar as [Benign]. Clinvar id is 256322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-94606869-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBP1	NM_000507.4	c.651C>T	p.Ala217=	synonymous_variant	5/7	ENST00000375326.9
FBP1	NM_001127628.2	c.651C>T	p.Ala217=	synonymous_variant	6/8
FBP1	XM_006717005.5	c.405C>T	p.Ala135=	synonymous_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBP1	ENST00000375326.9	c.651C>T	p.Ala217=	synonymous_variant	5/7	1	NM_000507.4	P1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47624 AN: 152056 Hom.: 7592 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.293

GnomAD3 exomes AF: 0.329 AC: 82659 AN: 251338 Hom.: 14801 AF XY: 0.333 AC XY: 45206 AN XY: 135844

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.188

Gnomad ASJ exome AF: 0.226

Gnomad EAS exome AF: 0.549

Gnomad SAS exome AF: 0.376

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.338 AC: 493510 AN: 1461176 Hom.: 86106 Cov.: 38 AF XY: 0.339 AC XY: 246236 AN XY: 726936

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.558

Gnomad4 SAS exome AF: 0.368

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.313 AC: 47671 AN: 152174 Hom.: 7599 Cov.: 32 AF XY: 0.313 AC XY: 23273 AN XY: 74376

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.297

Alfa AF: 0.316 Hom.: 4365

Bravo AF: 0.300

Asia WGS AF: 0.421 AC: 1461 AN: 3478

EpiCase AF: 0.323

EpiControl AF: 0.320

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Aug 30, 2012	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Fructose-biphosphatase deficiency Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	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:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs1042144; hg19: chr9-97369151; COSMIC: COSV64688735; COSMIC: COSV64688735;