rs2297084

Variant names:

• chr9-94606801-G-A
• rs2297084
• NM_000507.4:c.705+14C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• fructose-1,6-bisphosphatase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 256324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000507.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP1	NM_000507.4	MANE Select	c.705+14C>T		intron	N/A	NP_000498.2
	FBP1	NM_001127628.2		c.705+14C>T		intron	N/A	NP_001121100.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP1	ENST00000375326.9	TSL:1 MANE Select	c.705+14C>T		intron	N/A	ENSP00000364475.5
	FBP1	ENST00000884868.1		c.705+14C>T		intron	N/A	ENSP00000554927.1
	FBP1	ENST00000945615.1		c.705+14C>T		intron	N/A	ENSP00000615674.1

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

GnomAD2 exomes AF: 0.517 AC: 127174 AN: 246200 AF XY: 0.511

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 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

African (AFR) AF: 0.483 AC: 16131 AN: 33424

American (AMR) AF: 0.696 AC: 30808 AN: 44296

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 17169 AN: 26090

East Asian (EAS) AF: 0.391 AC: 15477 AN: 39622

South Asian (SAS) AF: 0.434 AC: 37386 AN: 86088

European-Finnish (FIN) AF: 0.426 AC: 22708 AN: 53298

Middle Eastern (MID) AF: 0.545 AC: 2952 AN: 5418

European-Non Finnish (NFE) AF: 0.504 AC: 559692 AN: 1109916

Other (OTH) AF: 0.522 AC: 31415 AN: 60236

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

African (AFR) AF: 0.478 AC: 19804 AN: 41474

American (AMR) AF: 0.633 AC: 9679 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2359 AN: 3470

East Asian (EAS) AF: 0.410 AC: 2110 AN: 5142

South Asian (SAS) AF: 0.431 AC: 2076 AN: 4822

European-Finnish (FIN) AF: 0.419 AC: 4428 AN: 10576

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.515 AC: 35016 AN: 67972

Other (OTH) AF: 0.536 AC: 1134 AN: 2116

Alfa AF: 0.541 Hom.: 4153

Bravo AF: 0.525

Asia WGS AF: 0.433 AC: 1506 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Fructose-biphosphatase deficiency (3)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.052
DANN	Benign	0.67
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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