dbSNP rs1539234: PFKFB3:c.*1838G>A (chr10-6234780-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004566.4(PFKFB3):c.*1838G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,138 control chromosomes in the GnomAD database, including 31,095 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.63 ( 31069 hom., cov: 30)

Exomes 𝑓: 0.60 ( 26 hom. )

Consequence

PFKFB3
NM_004566.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.189

Publications

12 publications found

Variant links:

Genes affected

PFKFB3 (HGNC:8874): (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3) The protein encoded by this gene belongs to a family of bifunctional proteins that are involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls glycolysis in eukaryotes. The encoded protein has a 6-phosphofructo-2-kinase activity that catalyzes the synthesis of fructose-2,6-bisphosphate (F2,6BP), and a fructose-2,6-biphosphatase activity that catalyzes the degradation of F2,6BP. This protein is required for cell cycle progression and prevention of apoptosis. It functions as a regulator of cyclin-dependent kinase 1, linking glucose metabolism to cell proliferation and survival in tumor cells. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

PFKFB3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFKFB3	NM_004566.4 link	c.*1838G>A		3_prime_UTR_variant	Exon 15 of 15	ENST00000379775.9	NP_004557.1	Q16875-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PFKFB3	ENST00000379775.9 link	c.*1838G>A	3_prime_UTR_variant	Exon 15 of 15	1	NM_004566.4	ENSP00000369100.4	Q16875-1
PFKFB3	ENST00000379789.8 link	c.*1838G>A	3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000369115.4	Q16875-3
PFKFB3	ENST00000360521.7 link	c.*1879G>A	3_prime_UTR_variant	Exon 16 of 16	5		ENSP00000353712.2	Q16875-2
PFKFB3	ENST00000640683.1 link	c.1515+8415G>A	intron_variant	Intron 14 of 14	5		ENSP00000492001.1	A0A1W2PR17

Frequencies

GnomAD3 genomes

AF:

0.626

AC:

95145

AN:

151870

Hom.:

31018

Cov.:

show subpopulations

Gnomad AFR

AF:

0.810

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.651

Gnomad EAS

AF:

0.536

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.618

Gnomad NFE

AF:

0.580

Gnomad OTH

AF:

0.600

GnomAD4 exome

AF:

0.601

AC:

AN:

148

Hom.:

Cov.:

AF XY:

0.628

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.618

AC:

AN:

136

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.417

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.627

AC:

95246

AN:

151990

Hom.:

31069

Cov.:

AF XY:

0.618

AC XY:

45918

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.810

AC:

33578

AN:

41454

American (AMR)

AF:

0.492

AC:

7501

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.651

AC:

2260

AN:

3472

East Asian (EAS)

AF:

0.536

AC:

2768

AN:

5164

South Asian (SAS)

AF:

0.524

AC:

2525

AN:

4816

European-Finnish (FIN)

AF:

0.511

AC:

5396

AN:

10554

Middle Eastern (MID)

AF:

0.620

AC:

181

AN:

292

European-Non Finnish (NFE)

AF:

0.580

AC:

39445

AN:

67966

Other (OTH)

AF:

0.600

AC:

1267

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1695

3389

5084

6778

8473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

764

1528

2292

3056

3820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.586

Hom.:

38605

Bravo

AF:

0.633

Asia WGS

AF:

0.500

AC:

1744

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

(source)

DANN

Benign

0.59

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over