rs4129220

Variant names:

• chr9-94627816-G-A
• rs4129220
• NM_000507.4:c.171-7325C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000507.4(FBP1):​c.171-7325C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,040 control chromosomes in the GnomAD database, including 10,186 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 0.36 (10186 hom., cov: 32)
• Consequence: FBP1 NM_000507.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431
• 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]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBP1	NM_000507.4	c.171-7325C>T		intron_variant	Intron 1 of 6	ENST00000375326.9	NP_000498.2
FBP1	NM_001127628.2	c.171-7325C>T		intron_variant	Intron 2 of 7		NP_001121100.1
FBP1	XM_006717005.5	c.-76-7325C>T		intron_variant	Intron 1 of 6		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9	c.171-7325C>T		intron_variant	Intron 1 of 6	1	NM_000507.4	ENSP00000364475.5

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55126 AN: 151922 Hom.: 10180 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.363 AC: 55160 AN: 152040 Hom.: 10186 Cov.: 32 AF XY: 0.359 AC XY: 26677 AN XY: 74316

African (AFR) AF: 0.352 AC: 14598 AN: 41474

American (AMR) AF: 0.425 AC: 6486 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1720 AN: 3472

East Asian (EAS) AF: 0.144 AC: 743 AN: 5156

South Asian (SAS) AF: 0.239 AC: 1148 AN: 4810

European-Finnish (FIN) AF: 0.325 AC: 3436 AN: 10576

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25634 AN: 67964

Other (OTH) AF: 0.382 AC: 804 AN: 2104

Alfa AF: 0.378 Hom.: 26846

Bravo AF: 0.371

Asia WGS AF: 0.220 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.81
DANN	Benign	0.27
PhyloP100		-0.43
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: rs4129220; hg19: chr9-97390098;