rs3020781

chr1-155299985-A-Gchr1-155299985-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.518

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
PKLR	NM_000298.6	c.283+113T>C		intron_variant		ENST00000342741.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKLR	ENST00000342741.6	c.283+113T>C		intron_variant		1	NM_000298.6	P3
PKLR	ENST00000392414.7	c.190+113T>C		intron_variant		1		A1
PKLR	ENST00000434082.3	c.91+113T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58665 AN: 151954 Hom.: 13282 Cov.: 31

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

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.: 31 AF XY: 0.387 AC XY: 28800 AN XY: 74338

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-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

Other links and lift over

dbSNP: rs3020781; hg19: chr1-155269776; COSMIC: COSV61362210;