rs8192689

Variant names:

• chr9-94617761-G-A
• rs8192689
• NM_000507.4:c.426+7C>T

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.426+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,590,510 control chromosomes in the GnomAD database, including 95,582 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (7989 hom., cov: 32)
  • Exomes 𝑓: 0.34 (87593 hom.)
• Consequence: FBP1 NM_000507.4 splice_region, intron
• Scores: Splicing: ADA: 0.0003523
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.387
• Publications: 16 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), Orphanet, Genomics England PanelApp, G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 9-94617761-G-A is Benign according to our data. Variant chr9-94617761-G-A is described in ClinVar as Benign. ClinVar VariationId is 256320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 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.426+7C>T		splice_region intron	N/A	NP_000498.2
	FBP1	NM_001127628.2		c.426+7C>T		splice_region intron	N/A	NP_001121100.1	P09467

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP1	ENST00000375326.9	TSL:1 MANE Select	c.426+7C>T		splice_region intron	N/A	ENSP00000364475.5	P09467
	FBP1	ENST00000884868.1		c.426+7C>T		splice_region intron	N/A	ENSP00000554927.1
	FBP1	ENST00000945615.1		c.426+7C>T		splice_region intron	N/A	ENSP00000615674.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48755 AN: 151770 Hom.: 7978 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.302

GnomAD2 exomes AF: 0.336 AC: 84275 AN: 250660 AF XY: 0.341

Gnomad AFR exome AF: 0.280

Gnomad AMR exome AF: 0.192

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.551

Gnomad FIN exome AF: 0.386

Gnomad NFE exome AF: 0.338

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.343 AC: 492730 AN: 1438622 Hom.: 87593 Cov.: 29 AF XY: 0.344 AC XY: 246727 AN XY: 717162

African (AFR) AF: 0.272 AC: 8981 AN: 33062

American (AMR) AF: 0.195 AC: 8697 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 6257 AN: 26032

East Asian (EAS) AF: 0.585 AC: 23140 AN: 39536

South Asian (SAS) AF: 0.383 AC: 32886 AN: 85754

European-Finnish (FIN) AF: 0.399 AC: 21231 AN: 53236

Middle Eastern (MID) AF: 0.241 AC: 1380 AN: 5724

European-Non Finnish (NFE) AF: 0.340 AC: 370543 AN: 1090986

Other (OTH) AF: 0.329 AC: 19615 AN: 59626

GnomAD4 genome AF: 0.321 AC: 48804 AN: 151888 Hom.: 7989 Cov.: 32 AF XY: 0.322 AC XY: 23877 AN XY: 74226

African (AFR) AF: 0.285 AC: 11787 AN: 41404

American (AMR) AF: 0.234 AC: 3565 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2858 AN: 5158

South Asian (SAS) AF: 0.392 AC: 1880 AN: 4800

European-Finnish (FIN) AF: 0.389 AC: 4096 AN: 10526

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22867 AN: 67968

Other (OTH) AF: 0.306 AC: 644 AN: 2104

Alfa AF: 0.317 Hom.: 12526

Bravo AF: 0.306

Asia WGS AF: 0.422 AC: 1465 AN: 3478

EpiCase AF: 0.329

EpiControl AF: 0.328

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Fructose-biphosphatase deficiency (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.41
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00035
dbscSNV1_RF	Benign	0.028
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: rs8192689; hg19: chr9-97380043; COSMIC: COSV107478007;