Variant chr1-155299985-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.283+113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,162,072 control chromosomes in the GnomAD database, including 65,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 13326 hom., cov: 31)

Exomes 𝑓: 0.30 ( 51873 hom. )

Consequence

PKLR
NM_000298.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.518

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=-1.0).

BP6

Variant 1-155299985-A-G is Benign according to our data. Variant chr1-155299985-A-G is described in ClinVar as [Benign]. Clinvar id is 1237051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-155299985-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKLR	NM_000298.6 linkuse as main transcript	c.283+113T>C		intron_variant		ENST00000342741.6	NP_000289.1	P30613-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PKLR	ENST00000342741.6 linkuse as main transcript	c.283+113T>C	intron_variant	1	NM_000298.6	ENSP00000339933.4	P30613-1
PKLR	ENST00000392414.7 linkuse as main transcript	c.190+113T>C	intron_variant	1		ENSP00000376214.3	P30613-2
PKLR	ENST00000434082.3 linkuse as main transcript	c.91+113T>C	intron_variant	5		ENSP00000398037.3	F8W6W2

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58665

AN:

151954

Hom.:

13282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.703

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.359

GnomAD4 exome

AF:

0.302

AC:

304565

AN:

1010000

Hom.:

51873

AF XY:

0.299

AC XY:

153134

AN XY:

512692

show subpopulations

Gnomad4 AFR exome

AF:

0.616

Gnomad4 AMR exome

AF:

0.413

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.726

Gnomad4 SAS exome

AF:

0.328

Gnomad4 FIN exome

AF:

0.305

Gnomad4 NFE exome

AF:

0.262

Gnomad4 OTH exome

AF:

0.313

GnomAD4 genome

AF:

0.386

AC:

58758

AN:

152072

Hom.:

13326

Cov.:

AF XY:

0.387

AC XY:

28800

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.608

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.222

Gnomad4 EAS

AF:

0.702

Gnomad4 SAS

AF:

0.340

Gnomad4 FIN

AF:

0.320

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.296

Hom.:

3790

Bravo

AF:

0.403

Asia WGS

AF:

0.546

AC:

1899

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	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

5.1

DANN

Benign

0.63

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