rs2274689

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_000507.4(FBP1):c.*121T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 833,908 control chromosomes in the GnomAD database, including 187 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 0.013 ( 25 hom., cov: 33)

Exomes 𝑓: 0.018 ( 162 hom. )

Consequence

FBP1
NM_000507.4 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.254

Publications

5 publications found

Variant links:

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 links:

PCAT7 (HGNC:48824): (prostate cancer associated transcript 7)

PCAT7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-94603260-A-C is Benign according to our data. Variant chr9-94603260-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 913848.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0132 (2009/152300) while in subpopulation SAS AF = 0.0296 (143/4824). AF 95% confidence interval is 0.0257. There are 25 homozygotes in GnomAd4. There are 997 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FBP1	NM_000507.4 link	c.*121T>G	3_prime_UTR_variant	Exon 7 of 7	ENST00000375326.9	NP_000498.2	P09467
FBP1	NM_001127628.2 link	c.*121T>G	3_prime_UTR_variant	Exon 8 of 8		NP_001121100.1	P09467Q2TU34
FBP1	XM_006717005.5 link	c.*121T>G	3_prime_UTR_variant	Exon 7 of 7		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9 link	c.*121T>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_000507.4	ENSP00000364475.5		P09467

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

2011

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00345

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.0729

Gnomad EAS

AF:

0.0187

Gnomad SAS

AF:

0.0302

Gnomad FIN

AF:

0.00659

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0158

Gnomad OTH

AF:

0.0187

GnomAD4 exome

AF:

0.0181

AC:

12349

AN:

681608

Hom.:

162

Cov.:

AF XY:

0.0189

AC XY:

6789

AN XY:

360002

show subpopulations

African (AFR)

AF:

0.00363

AC:

AN:

17896

American (AMR)

AF:

0.0110

AC:

380

AN:

34664

Ashkenazi Jewish (ASJ)

AF:

0.0614

AC:

1254

AN:

20432

East Asian (EAS)

AF:

0.0391

AC:

1271

AN:

32496

South Asian (SAS)

AF:

0.0275

AC:

1766

AN:

64120

European-Finnish (FIN)

AF:

0.00551

AC:

267

AN:

48482

Middle Eastern (MID)

AF:

0.0219

AC:

AN:

2688

European-Non Finnish (NFE)

AF:

0.0156

AC:

6637

AN:

426382

Other (OTH)

AF:

0.0189

AC:

650

AN:

34448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

602

1204

1807

2409

3011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0132

AC:

2009

AN:

152300

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

997

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00344

AC:

143

AN:

41564

American (AMR)

AF:

0.0114

AC:

175

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0729

AC:

253

AN:

3470

East Asian (EAS)

AF:

0.0189

AC:

AN:

5180

South Asian (SAS)

AF:

0.0296

AC:

143

AN:

4824

European-Finnish (FIN)

AF:

0.00659

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0158

AC:

1076

AN:

68026

Other (OTH)

AF:

0.0185

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

111

222

332

443

554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0174

Hom.:

Bravo

AF:

0.0125

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Fructose-biphosphatase deficiency

Uncertain:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Benign:1

Oct 27, 2020

GeneDx

Significance:Likely 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

-0.83

CADD

Benign

1.2

(source)

DANN

Benign

0.52

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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rs2274689

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over