rs4129219

chr9-94628006-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000507.4(FBP1):c.171-7515A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,146 control chromosomes in the GnomAD database, including 3,576 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3576 hom., cov: 32)
• Consequence: FBP1 NM_000507.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBP1	NM_000507.4	c.171-7515A>G		intron_variant		ENST00000375326.9
FBP1	NM_001127628.2	c.171-7515A>G		intron_variant
FBP1	XM_006717005.5	c.-76-7515A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBP1	ENST00000375326.9	c.171-7515A>G		intron_variant		1	NM_000507.4	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31316 AN: 152028 Hom.: 3573 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.207

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.206 AC: 31337 AN: 152146 Hom.: 3576 Cov.: 32 AF XY: 0.210 AC XY: 15584 AN XY: 74382

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.209

Alfa AF: 0.171 Hom.: 4887

Bravo AF: 0.219

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.9
Dann	Benign	0.63

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: rs4129219; hg19: chr9-97390288;