rs2070755

chr20-57562984-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002591.4(PCK1):c.611-44G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,587,932 control chromosomes in the GnomAD database, including 192,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (16952 hom., cov: 34)
  • Exomes 𝑓: 0.49 (175100 hom.)
• Consequence: PCK1 NM_002591.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.543

Genes affected

PCK1 (HGNC:8724): (phosphoenolpyruvate carboxykinase 1) This gene is a main control point for the regulation of gluconeogenesis. The cytosolic enzyme encoded by this gene, along with GTP, catalyzes the formation of phosphoenolpyruvate from oxaloacetate, with the release of carbon dioxide and GDP. The expression of this gene can be regulated by insulin, glucocorticoids, glucagon, cAMP, and diet. Defects in this gene are a cause of cytosolic phosphoenolpyruvate carboxykinase deficiency. A mitochondrial isozyme of the encoded protein also has been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-57562984-G-C is Benign according to our data. Variant chr20-57562984-G-C is described in ClinVar as [Benign]. Clinvar id is 1234699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCK1	NM_002591.4	c.611-44G>C		intron_variant		ENST00000319441.6
PCK1	XM_024451888.2	c.215-44G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCK1	ENST00000319441.6	c.611-44G>C		intron_variant		1	NM_002591.4	P1
PCK1	ENST00000467047.1	n.1905G>C		non_coding_transcript_exon_variant	1/2	1
PCK1	ENST00000470051.1	n.151G>C		non_coding_transcript_exon_variant	1/2	2
PCK1	ENST00000498194.1	n.553-44G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.467 AC: 71038 AN: 152082 Hom.: 16943 Cov.: 34

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.495

GnomAD3 exomes AF: 0.469 AC: 114321 AN: 243830 Hom.: 27251 AF XY: 0.468 AC XY: 61818 AN XY: 131984

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.499

Gnomad EAS exome AF: 0.305

Gnomad SAS exome AF: 0.406

Gnomad FIN exome AF: 0.506

Gnomad NFE exome AF: 0.498

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.491 AC: 705214 AN: 1435732 Hom.: 175100 Cov.: 29 AF XY: 0.489 AC XY: 348376 AN XY: 712504

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.408

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.503

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.467 AC: 71071 AN: 152200 Hom.: 16952 Cov.: 34 AF XY: 0.467 AC XY: 34734 AN XY: 74420

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.498

Alfa AF: 0.478 Hom.: 3206

Bravo AF: 0.466

Asia WGS AF: 0.381 AC: 1325 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Phosphoenolpyruvate carboxykinase deficiency, cytosolic Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.58
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2070755; hg19: chr20-56138040; COSMIC: COSV60126011; COSMIC: COSV60126011;