9-94603587-C-T

Variant names:

• chr9-94603587-C-T
• rs148942437
• NM_000507.4:c.826-15G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_000507.4(FBP1):​c.826-15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,612,962 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0065 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (14 hom.)
• Consequence: FBP1 NM_000507.4 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 0.409
• Publications: 4 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]

PCAT7 (HGNC:48824): (prostate cancer associated transcript 7)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-94603587-C-T is Benign according to our data. Variant chr9-94603587-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 137366.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00648 (987/152234) while in subpopulation AFR AF = 0.0227 (945/41542). AF 95% confidence interval is 0.0215. There are 14 homozygotes in GnomAd4. There are 465 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

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.826-15G>A		intron	N/A	NP_000498.2
	FBP1	NM_001127628.2		c.826-15G>A		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.826-15G>A		intron	N/A	ENSP00000364475.5	P09467
	FBP1	ENST00000884868.1		c.979G>A	p.Gly327Ser	missense	Exon 8 of 8	ENSP00000554927.1
	FBP1	ENST00000945615.1		c.979G>A	p.Gly327Ser	missense	Exon 7 of 7	ENSP00000615674.1

Frequencies

GnomAD3 genomes AF: 0.00645 AC: 981 AN: 152116 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00177 AC: 446 AN: 251454 AF XY: 0.00129

Gnomad AFR exome AF: 0.0222

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000237

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000728 AC: 1064 AN: 1460728 Hom.: 14 Cov.: 34 AF XY: 0.000644 AC XY: 468 AN XY: 726816

African (AFR) AF: 0.0247 AC: 825 AN: 33438

American (AMR) AF: 0.00125 AC: 56 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5762

European-Non Finnish (NFE) AF: 0.0000756 AC: 84 AN: 1111008

Other (OTH) AF: 0.00134 AC: 81 AN: 60350

GnomAD4 genome AF: 0.00648 AC: 987 AN: 152234 Hom.: 14 Cov.: 32 AF XY: 0.00625 AC XY: 465 AN XY: 74454

African (AFR) AF: 0.0227 AC: 945 AN: 41542

American (AMR) AF: 0.00177 AC: 27 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67994

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.000677 Hom.: 0

Bravo AF: 0.00722

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.54
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs148942437; hg19: chr9-97365869;