rs201591116

Variant names:

• chr9-94620425-G-A
• rs201591116
• NM_000507.4:c.237C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-94620425-G-A
• chr9-94620425-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BS1 BS2

The NM_000507.4(FBP1):​c.237C>T​(p.Asn79Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,614,158 control chromosomes in the GnomAD database, including 30 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 0.0019 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (24 hom.)
• Consequence: FBP1 NM_000507.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 0.921
• Publications: 2 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 9-94620425-G-A is Benign according to our data. Variant chr9-94620425-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 137363.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0019 (290/152296) while in subpopulation EAS AF = 0.00559 (29/5186). AF 95% confidence interval is 0.004. There are 6 homozygotes in GnomAd4. There are 191 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 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.237C>T	p.Asn79Asn	synonymous	Exon 2 of 7	NP_000498.2
	FBP1	NM_001127628.2		c.237C>T	p.Asn79Asn	synonymous	Exon 3 of 8	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.237C>T	p.Asn79Asn	synonymous	Exon 2 of 7	ENSP00000364475.5	P09467
	FBP1	ENST00000414122.1	TSL:5	c.-16C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000411619.1	Q5VZC3
	FBP1	ENST00000884868.1		c.237C>T	p.Asn79Asn	synonymous	Exon 3 of 8	ENSP00000554927.1

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 290 AN: 152178 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00558

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00262 AC: 658 AN: 251476 AF XY: 0.00248

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00386

Gnomad FIN exome AF: 0.0221

Gnomad NFE exome AF: 0.000527

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00116 AC: 1700 AN: 1461862 Hom.: 24 Cov.: 32 AF XY: 0.00115 AC XY: 839 AN XY: 727234

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00194 AC: 77 AN: 39700

South Asian (SAS) AF: 0.00104 AC: 90 AN: 86256

European-Finnish (FIN) AF: 0.0236 AC: 1260 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000155 AC: 172 AN: 1111982

Other (OTH) AF: 0.00156 AC: 94 AN: 60396

GnomAD4 genome AF: 0.00190 AC: 290 AN: 152296 Hom.: 6 Cov.: 32 AF XY: 0.00257 AC XY: 191 AN XY: 74462

African (AFR) AF: 0.0000241 AC: 1 AN: 41550

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

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

East Asian (EAS) AF: 0.00559 AC: 29 AN: 5186

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4826

European-Finnish (FIN) AF: 0.0196 AC: 208 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68030

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000449 Hom.: 1

Bravo AF: 0.000242

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.9
DANN	Benign	0.70
PhyloP100		0.92
Mutation Taster		=99/1	polymorphism

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: rs201591116; hg19: chr9-97382707; COSMIC: COSV64689325;