chr1-207071700-T-C

Position:

• chr1-207071700-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006212.2(PFKFB2):​c.1350+127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 679,684 control chromosomes in the GnomAD database, including 81,694 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 0.45 (15822 hom., cov: 32)
  • Exomes 𝑓: 0.49 (65872 hom.)
• Consequence: PFKFB2 NM_006212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFKFB2	NM_006212.2	c.1350+127T>C		intron_variant		ENST00000367080.8	NP_006203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFKFB2	ENST00000367080.8	c.1350+127T>C		intron_variant		1	NM_006212.2	ENSP00000356047

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67641 AN: 151952 Hom.: 15816 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.413

GnomAD4 exome AF: 0.490 AC: 258425 AN: 527614 Hom.: 65872 AF XY: 0.492 AC XY: 137383 AN XY: 279392

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.569

Gnomad4 ASJ exome AF: 0.399

Gnomad4 EAS exome AF: 0.762

Gnomad4 SAS exome AF: 0.536

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.464

GnomAD4 genome AF: 0.445 AC: 67683 AN: 152070 Hom.: 15822 Cov.: 32 AF XY: 0.449 AC XY: 33335 AN XY: 74318

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.414

Alfa AF: 0.469 Hom.: 3404

Bravo AF: 0.442

Asia WGS AF: 0.643 AC: 2234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.23

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

LitVar

Other links and lift over

dbSNP: rs11120137; hg19: chr1-207245045;