9-94609890-C-T

Variant names:

• chr9-94609890-C-T
• rs3739747
• NM_000507.4:c.567+31G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000507.4(FBP1):​c.567+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,611,142 control chromosomes in the GnomAD database, including 144,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12884 hom., cov: 31)
  • Exomes 𝑓: 0.42 (131416 hom.)
• Consequence: FBP1 NM_000507.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.206
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-94609890-C-T is Benign according to our data. Variant chr9-94609890-C-T is described in ClinVar as Benign. ClinVar VariationId is 256321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBP1	NM_000507.4	c.567+31G>A		intron_variant	Intron 4 of 6	ENST00000375326.9	NP_000498.2
FBP1	NM_001127628.2	c.567+31G>A		intron_variant	Intron 5 of 7		NP_001121100.1
FBP1	XM_006717005.5	c.321+31G>A		intron_variant	Intron 4 of 6		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9	c.567+31G>A		intron_variant	Intron 4 of 6	1	NM_000507.4	ENSP00000364475.5

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61709 AN: 151764 Hom.: 12879 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.439

GnomAD2 exomes AF: 0.407 AC: 101267 AN: 248734 AF XY: 0.405

Gnomad AFR exome AF: 0.332

Gnomad AMR exome AF: 0.507

Gnomad ASJ exome AF: 0.553

Gnomad EAS exome AF: 0.170

Gnomad FIN exome AF: 0.384

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.437

GnomAD4 exome AF: 0.420 AC: 612549 AN: 1459258 Hom.: 131416 Cov.: 34 AF XY: 0.417 AC XY: 303046 AN XY: 726076

African (AFR) AF: 0.340 AC: 11373 AN: 33424

American (AMR) AF: 0.511 AC: 22841 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 14426 AN: 26118

East Asian (EAS) AF: 0.214 AC: 8491 AN: 39680

South Asian (SAS) AF: 0.307 AC: 26492 AN: 86196

European-Finnish (FIN) AF: 0.381 AC: 20355 AN: 53398

Middle Eastern (MID) AF: 0.439 AC: 2422 AN: 5518

European-Non Finnish (NFE) AF: 0.433 AC: 480792 AN: 1109968

Other (OTH) AF: 0.421 AC: 25357 AN: 60254

GnomAD4 genome AF: 0.406 AC: 61737 AN: 151884 Hom.: 12884 Cov.: 31 AF XY: 0.403 AC XY: 29945 AN XY: 74266

African (AFR) AF: 0.337 AC: 13962 AN: 41384

American (AMR) AF: 0.488 AC: 7452 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2027 AN: 3472

East Asian (EAS) AF: 0.190 AC: 978 AN: 5146

South Asian (SAS) AF: 0.296 AC: 1426 AN: 4820

European-Finnish (FIN) AF: 0.375 AC: 3959 AN: 10552

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30303 AN: 67928

Other (OTH) AF: 0.433 AC: 915 AN: 2112

Alfa AF: 0.442 Hom.: 4323

Bravo AF: 0.412

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fructose-biphosphatase deficiency Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.7
DANN	Benign	0.81
PhyloP100		-0.21
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: rs3739747; hg19: chr9-97372172; COSMIC: COSV64689338;