rs1769257

Variant names:

• chr9-94603438-T-C
• rs1769257
• NM_000507.4:c.960A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-94603438-T-C
• chr9-94603438-T-A
• chr9-94603438-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000507.4(FBP1):​c.960A>G​(p.Gly320Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 1,613,744 control chromosomes in the GnomAD database, including 586,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (59897 hom., cov: 29)
  • Exomes 𝑓: 0.85 (526322 hom.)
• Consequence: FBP1 NM_000507.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.565
• Publications: 25 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 9-94603438-T-C is Benign according to our data. Variant chr9-94603438-T-C is described in ClinVar as Benign. ClinVar VariationId is 256326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.565 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 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.960A>G	p.Gly320Gly	synonymous	Exon 7 of 7	NP_000498.2
	FBP1	NM_001127628.2		c.960A>G	p.Gly320Gly	synonymous	Exon 8 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.960A>G	p.Gly320Gly	synonymous	Exon 7 of 7	ENSP00000364475.5	P09467
	FBP1	ENST00000884868.1		c.1128A>G	p.Gly376Gly	synonymous	Exon 8 of 8	ENSP00000554927.1
	FBP1	ENST00000945615.1		c.1128A>G	p.Gly376Gly	synonymous	Exon 7 of 7	ENSP00000615674.1

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134553 AN: 151982 Hom.: 59837 Cov.: 29

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.915

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.833

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.876

GnomAD2 exomes AF: 0.863 AC: 216541 AN: 251062 AF XY: 0.857

Gnomad AFR exome AF: 0.968

Gnomad AMR exome AF: 0.898

Gnomad ASJ exome AF: 0.886

Gnomad EAS exome AF: 0.956

Gnomad FIN exome AF: 0.806

Gnomad NFE exome AF: 0.846

Gnomad OTH exome AF: 0.854

GnomAD4 exome AF: 0.848 AC: 1239378 AN: 1461644 Hom.: 526322 Cov.: 54 AF XY: 0.846 AC XY: 615367 AN XY: 727102

African (AFR) AF: 0.967 AC: 32383 AN: 33478

American (AMR) AF: 0.899 AC: 40188 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 23135 AN: 26134

East Asian (EAS) AF: 0.953 AC: 37815 AN: 39700

South Asian (SAS) AF: 0.803 AC: 69290 AN: 86240

European-Finnish (FIN) AF: 0.814 AC: 43495 AN: 53418

Middle Eastern (MID) AF: 0.777 AC: 4479 AN: 5766

European-Non Finnish (NFE) AF: 0.842 AC: 936630 AN: 1111810

Other (OTH) AF: 0.861 AC: 51963 AN: 60384

GnomAD4 genome AF: 0.885 AC: 134673 AN: 152100 Hom.: 59897 Cov.: 29 AF XY: 0.880 AC XY: 65418 AN XY: 74330

African (AFR) AF: 0.967 AC: 40148 AN: 41512

American (AMR) AF: 0.886 AC: 13522 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3124 AN: 3472

East Asian (EAS) AF: 0.959 AC: 4948 AN: 5158

South Asian (SAS) AF: 0.811 AC: 3889 AN: 4794

European-Finnish (FIN) AF: 0.795 AC: 8419 AN: 10584

Middle Eastern (MID) AF: 0.831 AC: 241 AN: 290

European-Non Finnish (NFE) AF: 0.848 AC: 57698 AN: 68006

Other (OTH) AF: 0.878 AC: 1851 AN: 2108

Alfa AF: 0.865 Hom.: 32121

Bravo AF: 0.896

Asia WGS AF: 0.873 AC: 3034 AN: 3478

EpiCase AF: 0.847

EpiControl AF: 0.842

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Fructose-biphosphatase deficiency (4)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.1
DANN	Benign	0.50
PhyloP100		-0.56
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: rs1769257; hg19: chr9-97365720; COSMIC: COSV64688733; COSMIC: COSV64688733;