1-207079302-T-A

Variant names:

• chr1-207079302-T-A
• rs17258746
• ENST00000367079.3:c.*283T>A

Variant summary

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

The ENST00000367079.3(PFKFB2):​c.*283T>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 0.125 in 518,216 control chromosomes in the GnomAD database, including 4,286 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 (1089 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3197 hom.)
• Consequence: PFKFB2 ENST00000367079.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 15 publications found

Genes affected

PFKFB2 (HGNC:8873): (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2) The protein encoded by this gene is 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, and a fructose-2,6-biphosphatase activity that catalyzes the degradation of fructose-2,6-bisphosphate. This protein regulates fructose-2,6-bisphosphate levels in the heart, while a related enzyme encoded by a different gene regulates fructose-2,6-bisphosphate levels in the liver and muscle. This enzyme functions as a homodimer. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367079.3. 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
	PFKFB2	NM_001018053.2		c.*283T>A		3_prime_UTR	Exon 15 of 15	NP_001018063.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKFB2	ENST00000367079.3	TSL:1	c.*283T>A		3_prime_UTR	Exon 15 of 15	ENSP00000356046.2
	PFKFB2	ENST00000473310.5	TSL:2	n.519T>A		non_coding_transcript_exon	Exon 3 of 3
	PFKFB2	ENST00000411990.6	TSL:2	n.*1481T>A		downstream_gene	N/A	ENSP00000408717.3

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17336 AN: 152132 Hom.: 1087 Cov.: 32

Gnomad AFR AF: 0.0591

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.129 AC: 47386 AN: 365966 Hom.: 3197 Cov.: 0 AF XY: 0.129 AC XY: 24772 AN XY: 192598

African (AFR) AF: 0.0572 AC: 609 AN: 10642

American (AMR) AF: 0.146 AC: 2169 AN: 14900

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 1435 AN: 11278

East Asian (EAS) AF: 0.117 AC: 2830 AN: 24156

South Asian (SAS) AF: 0.109 AC: 4424 AN: 40404

European-Finnish (FIN) AF: 0.136 AC: 3103 AN: 22876

Middle Eastern (MID) AF: 0.160 AC: 259 AN: 1614

European-Non Finnish (NFE) AF: 0.137 AC: 29872 AN: 218732

Other (OTH) AF: 0.126 AC: 2685 AN: 21364

GnomAD4 genome AF: 0.114 AC: 17338 AN: 152250 Hom.: 1089 Cov.: 32 AF XY: 0.115 AC XY: 8550 AN XY: 74440

African (AFR) AF: 0.0590 AC: 2452 AN: 41560

American (AMR) AF: 0.158 AC: 2415 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3470

East Asian (EAS) AF: 0.0902 AC: 467 AN: 5180

South Asian (SAS) AF: 0.110 AC: 530 AN: 4824

European-Finnish (FIN) AF: 0.131 AC: 1390 AN: 10598

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9204 AN: 67996

Other (OTH) AF: 0.138 AC: 293 AN: 2116

Alfa AF: 0.0640 Hom.: 65

Bravo AF: 0.112

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.5
DANN	Benign	0.86
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17258746; hg19: chr1-207252647; COSMIC: COSV107459513; COSMIC: COSV107459513;