Variant 1-155295386-A-G 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_000298.6(PKLR):c.507+51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,612,016 control chromosomes in the GnomAD database, including 84,128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 13507 hom., cov: 33)

Exomes 𝑓: 0.29 ( 70621 hom. )

Consequence

PKLR
NM_000298.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.49

Variant links:

Genes affected

PKLR (HGNC:9020): (pyruvate kinase L/R) The protein encoded by this gene is a pyruvate kinase that catalyzes the transphosphorylation of phohsphoenolpyruvate into pyruvate and ATP, which is the rate-limiting step of glycolysis. Defects in this enzyme, due to gene mutations or genetic variations, are the common cause of chronic hereditary nonspherocytic hemolytic anemia (CNSHA or HNSHA). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PKLR 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=-0.92).

BP6

Variant 1-155295386-A-G is Benign according to our data. Variant chr1-155295386-A-G is described in ClinVar as [Benign]. Clinvar id is 1280101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-155295386-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKLR	NM_000298.6 link	c.507+51T>C		intron_variant		ENST00000342741.6	NP_000289.1	P30613-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PKLR	ENST00000342741.6 link	c.507+51T>C	intron_variant	1	NM_000298.6	ENSP00000339933.4	P30613-1
PKLR	ENST00000392414.7 link	c.414+51T>C	intron_variant	1		ENSP00000376214.3	P30613-2
PKLR	ENST00000434082.3 link	c.315+51T>C	intron_variant	5		ENSP00000398037.3	F8W6W2

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58981

AN:

151914

Hom.:

13456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.702

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.363

GnomAD3 exomes

AF:

0.348

AC:

83521

AN:

240092

Hom.:

16792

AF XY:

0.335

AC XY:

43989

AN XY:

131390

show subpopulations

Gnomad AFR exome

AF:

0.627

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.703

Gnomad SAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.316

Gnomad NFE exome

AF:

0.253

Gnomad OTH exome

AF:

0.307

GnomAD4 exome

AF:

0.295

AC:

430522

AN:

1459986

Hom.:

70621

Cov.:

AF XY:

0.292

AC XY:

212366

AN XY:

726308

show subpopulations

Gnomad4 AFR exome

AF:

0.621

Gnomad4 AMR exome

AF:

0.413

Gnomad4 ASJ exome

AF:

0.223

Gnomad4 EAS exome

AF:

0.725

Gnomad4 SAS exome

AF:

0.329

Gnomad4 FIN exome

AF:

0.308

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.389

AC:

59083

AN:

152030

Hom.:

13507

Cov.:

AF XY:

0.390

AC XY:

28953

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.614

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.211

Gnomad4 EAS

AF:

0.701

Gnomad4 SAS

AF:

0.342

Gnomad4 FIN

AF:

0.323

Gnomad4 NFE

AF:

0.265

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.218

Hom.:

716

Bravo

AF:

0.405

Asia WGS

AF:

0.546

AC:

1898

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.017

DANN

Benign

0.12

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

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