rs1042144

Variant names:

• chr9-94606869-G-A
• rs1042144
• NM_000507.4:c.651C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-94606869-G-A
• chr9-94606869-G-C
• chr9-94606869-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000507.4(FBP1):​c.651C>T​(p.Ala217Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,613,350 control chromosomes in the GnomAD database, including 93,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7599 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86106 hom.)
• Consequence: FBP1 NM_000507.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 2.19
• Publications: 22 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 9-94606869-G-A is Benign according to our data. Variant chr9-94606869-G-A is described in ClinVar as Benign. ClinVar VariationId is 256322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 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.651C>T	p.Ala217Ala	synonymous	Exon 5 of 7	NP_000498.2
	FBP1	NM_001127628.2		c.651C>T	p.Ala217Ala	synonymous	Exon 6 of 8	NP_001121100.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP1	ENST00000375326.9	TSL:1 MANE Select	c.651C>T	p.Ala217Ala	synonymous	Exon 5 of 7	ENSP00000364475.5
	FBP1	ENST00000884868.1		c.651C>T	p.Ala217Ala	synonymous	Exon 6 of 8	ENSP00000554927.1
	FBP1	ENST00000945615.1		c.651C>T	p.Ala217Ala	synonymous	Exon 5 of 7	ENSP00000615674.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47624 AN: 152056 Hom.: 7592 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.293

GnomAD2 exomes AF: 0.329 AC: 82659 AN: 251338 AF XY: 0.333

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.188

Gnomad ASJ exome AF: 0.226

Gnomad EAS exome AF: 0.549

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.338 AC: 493510 AN: 1461176 Hom.: 86106 Cov.: 38 AF XY: 0.339 AC XY: 246236 AN XY: 726936

African (AFR) AF: 0.264 AC: 8821 AN: 33466

American (AMR) AF: 0.190 AC: 8501 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5910 AN: 26126

East Asian (EAS) AF: 0.558 AC: 22149 AN: 39696

South Asian (SAS) AF: 0.368 AC: 31741 AN: 86236

European-Finnish (FIN) AF: 0.388 AC: 20736 AN: 53412

Middle Eastern (MID) AF: 0.222 AC: 1276 AN: 5750

European-Non Finnish (NFE) AF: 0.337 AC: 374853 AN: 1111410

Other (OTH) AF: 0.323 AC: 19523 AN: 60364

GnomAD4 genome AF: 0.313 AC: 47671 AN: 152174 Hom.: 7599 Cov.: 32 AF XY: 0.313 AC XY: 23273 AN XY: 74376

African (AFR) AF: 0.272 AC: 11296 AN: 41542

American (AMR) AF: 0.230 AC: 3518 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 761 AN: 3466

East Asian (EAS) AF: 0.541 AC: 2789 AN: 5156

South Asian (SAS) AF: 0.377 AC: 1817 AN: 4820

European-Finnish (FIN) AF: 0.378 AC: 4001 AN: 10578

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.332 AC: 22562 AN: 67996

Other (OTH) AF: 0.297 AC: 629 AN: 2116

Alfa AF: 0.319 Hom.: 5819

Bravo AF: 0.300

Asia WGS AF: 0.421 AC: 1461 AN: 3478

EpiCase AF: 0.323

EpiControl AF: 0.320

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		2.2
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs1042144; hg19: chr9-97369151; COSMIC: COSV64688735; COSMIC: COSV64688735;