rs16910744

Variant names:

• chr9-94620386-C-A
• rs16910744
• NM_000507.4:c.276G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-94620386-C-A
• chr9-94620386-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BA1

The NM_000507.4(FBP1):​c.276G>T​(p.Thr92Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00944 in 1,614,140 control chromosomes in the GnomAD database, including 1,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T92T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.046 (551 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (519 hom.)
• Consequence: FBP1 NM_000507.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.141
• Publications: 6 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BP6: Variant 9-94620386-C-A is Benign according to our data. Variant chr9-94620386-C-A is described in ClinVar as Benign. ClinVar VariationId is 137364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.141 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 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.276G>T	p.Thr92Thr	synonymous	Exon 2 of 7	NP_000498.2
	FBP1	NM_001127628.2		c.276G>T	p.Thr92Thr	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.276G>T	p.Thr92Thr	synonymous	Exon 2 of 7	ENSP00000364475.5	P09467
	FBP1	ENST00000884868.1		c.276G>T	p.Thr92Thr	synonymous	Exon 3 of 8	ENSP00000554927.1
	FBP1	ENST00000945615.1		c.276G>T	p.Thr92Thr	synonymous	Exon 2 of 7	ENSP00000615674.1

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7039 AN: 152144 Hom.: 544 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0315

GnomAD2 exomes AF: 0.0132 AC: 3330 AN: 251484 AF XY: 0.00981

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.0109

Gnomad ASJ exome AF: 0.00565

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00134

Gnomad OTH exome AF: 0.00879

GnomAD4 exome AF: 0.00559 AC: 8166 AN: 1461878 Hom.: 519 Cov.: 32 AF XY: 0.00491 AC XY: 3571 AN XY: 727238

African (AFR) AF: 0.165 AC: 5509 AN: 33474

American (AMR) AF: 0.0114 AC: 508 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00478 AC: 125 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000406 AC: 35 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.0137 AC: 79 AN: 5768

European-Non Finnish (NFE) AF: 0.00104 AC: 1157 AN: 1112006

Other (OTH) AF: 0.0124 AC: 751 AN: 60394

GnomAD4 genome AF: 0.0465 AC: 7077 AN: 152262 Hom.: 551 Cov.: 32 AF XY: 0.0439 AC XY: 3268 AN XY: 74454

African (AFR) AF: 0.159 AC: 6599 AN: 41510

American (AMR) AF: 0.0199 AC: 305 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00116 AC: 79 AN: 68026

Other (OTH) AF: 0.0312 AC: 66 AN: 2116

Alfa AF: 0.0217 Hom.: 153

Bravo AF: 0.0532

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.00142

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	5.4
DANN	Benign	0.65
PhyloP100		-0.14
Mutation Taster		=91/9	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: rs16910744; hg19: chr9-97382668;