Variant rs2070755 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.543

Variant links:

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]

PCK1 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
PCK1	NM_002591.4 linkuse as main transcript	c.611-44G>C		intron_variant		ENST00000319441.6	NP_002582.3
PCK1	XM_024451888.2 linkuse as main transcript	c.215-44G>C		intron_variant			XP_024307656.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCK1	ENST00000319441.6 linkuse as main transcript	c.611-44G>C	intron_variant		1	NM_002591.4	ENSP00000319814	P1	P35558-1
PCK1	ENST00000467047.1 linkuse as main transcript	n.1905G>C	non_coding_transcript_exon_variant	1/2	1
PCK1	ENST00000470051.1 linkuse as main transcript	n.151G>C	non_coding_transcript_exon_variant	1/2	2
PCK1	ENST00000498194.1 linkuse as main transcript	n.553-44G>C	intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

71038

AN:

152082

Hom.:

16943

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.489

AC XY:

348376

AN XY:

712504

show subpopulations

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.:

AF XY:

0.467

AC XY:

34734

AN XY:

74420

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	- -

Phosphoenolpyruvate carboxykinase deficiency, cytosolic

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over