rs2185691

Variant names:

• chr10-6250644-T-C
• rs2185691
• NM_001363545.2:c.1516-3534T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363545.2(PFKFB3):​c.1516-3534T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 151,694 control chromosomes in the GnomAD database, including 1,169 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 0.11 (1169 hom., cov: 30)
• Consequence: PFKFB3 NM_001363545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 2 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363545.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKFB3	NM_001363545.2		c.1516-3534T>C		intron	N/A	NP_001350474.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKFB3	ENST00000640683.1	TSL:5	c.1516-3534T>C		intron	N/A	ENSP00000492001.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16390 AN: 151604 Hom.: 1164 Cov.: 30

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.104

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.108 AC: 16427 AN: 151694 Hom.: 1169 Cov.: 30 AF XY: 0.112 AC XY: 8310 AN XY: 74096

African (AFR) AF: 0.177 AC: 7295 AN: 41254

American (AMR) AF: 0.177 AC: 2694 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3466

East Asian (EAS) AF: 0.120 AC: 619 AN: 5162

South Asian (SAS) AF: 0.201 AC: 963 AN: 4786

European-Finnish (FIN) AF: 0.0353 AC: 372 AN: 10530

Middle Eastern (MID) AF: 0.107 AC: 31 AN: 290

European-Non Finnish (NFE) AF: 0.0593 AC: 4032 AN: 67954

Other (OTH) AF: 0.105 AC: 223 AN: 2114

Alfa AF: 0.0806 Hom.: 1710

Bravo AF: 0.120

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.3
DANN	Benign	0.66
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs2185691; hg19: chr10-6292607;