rs2179706

Positions:

• chr20-57564815-C-T

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.1318+202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 619,532 control chromosomes in the GnomAD database, including 68,335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15388 hom., cov: 33)
  • Exomes 𝑓: 0.47 (52947 hom.)
• Consequence: PCK1 NM_002591.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.635

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=-0.9).
• BP6: Variant 20-57564815-C-T is Benign according to our data. Variant chr20-57564815-C-T is described in ClinVar as [Benign]. Clinvar id is 1269048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCK1	NM_002591.4	c.1318+202C>T		intron_variant		ENST00000319441.6
PCK1	XM_024451888.2	c.922+202C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCK1	ENST00000319441.6	c.1318+202C>T		intron_variant		1	NM_002591.4	P1
PCK1	ENST00000467047.1	n.3736C>T		non_coding_transcript_exon_variant	1/2	1
PCK1	ENST00000485958.1	n.442+202C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67670 AN: 151984 Hom.: 15377 Cov.: 33

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.430

GnomAD4 exome AF: 0.471 AC: 220116 AN: 467430 Hom.: 52947 Cov.: 5 AF XY: 0.467 AC XY: 114521 AN XY: 245124

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.443

Gnomad4 EAS exome AF: 0.651

Gnomad4 SAS exome AF: 0.411

Gnomad4 FIN exome AF: 0.476

Gnomad4 NFE exome AF: 0.466

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.445 AC: 67730 AN: 152102 Hom.: 15388 Cov.: 33 AF XY: 0.448 AC XY: 33291 AN XY: 74344

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.431

Alfa AF: 0.457 Hom.: 22105

Bravo AF: 0.445

Asia WGS AF: 0.537 AC: 1870 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.90
CADD	Benign	0.41
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: rs2179706; hg19: chr20-56139871;