Variant rs2227891 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002862.4(PYGB):c.1504G>A(p.Asp502Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,611,656 control chromosomes in the GnomAD database, including 26,114 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2156 hom., cov: 33)

Exomes 𝑓: 0.18 ( 23958 hom. )

Consequence

PYGB
NM_002862.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.98

Variant links:

Genes affected

PYGB (HGNC:9723): (glycogen phosphorylase B) The protein encoded by this gene is a glycogen phosphorylase found predominantly in the brain. The encoded protein forms homodimers which can associate into homotetramers, the enzymatically active form of glycogen phosphorylase. The activity of this enzyme is positively regulated by AMP and negatively regulated by ATP, ADP, and glucose-6-phosphate. This enzyme catalyzes the rate-determining step in glycogen degradation. [provided by RefSeq, Jul 2008]

PYGB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013472438).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYGB	NM_002862.4 linkuse as main transcript	c.1504G>A	p.Asp502Asn	missense_variant	12/20	ENST00000216962.9	NP_002853.2	P11216
PYGB	XM_047440342.1 linkuse as main transcript	c.1504G>A	p.Asp502Asn	missense_variant	12/16		XP_047296298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYGB	ENST00000216962.9 linkuse as main transcript	c.1504G>A	p.Asp502Asn	missense_variant	12/20	1	NM_002862.4	ENSP00000216962.3		P11216

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23774

AN:

152104

Hom.:

2151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0772

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.0979

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.144

GnomAD3 exomes

AF:

0.169

AC:

42262

AN:

250324

Hom.:

3988

AF XY:

0.164

AC XY:

22243

AN XY:

135392

show subpopulations

Gnomad AFR exome

AF:

0.0764

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.0945

Gnomad EAS exome

AF:

0.336

Gnomad SAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.176

AC:

257201

AN:

1459434

Hom.:

23958

Cov.:

AF XY:

0.174

AC XY:

126214

AN XY:

726070

show subpopulations

Gnomad4 AFR exome

AF:

0.0744

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.0928

Gnomad4 EAS exome

AF:

0.328

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.189

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.156

AC:

23778

AN:

152222

Hom.:

2156

Cov.:

AF XY:

0.157

AC XY:

11652

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0770

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.0979

Gnomad4 EAS

AF:

0.343

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.191

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.173

Hom.:

2547

Bravo

AF:

0.150

TwinsUK

AF:

0.194

AC:

720

ALSPAC

AF:

0.178

AC:

685

ESP6500AA

AF:

0.0793

AC:

349

ESP6500EA

AF:

0.185

AC:

1593

ExAC

AF:

0.166

AC:

20195

Asia WGS

AF:

0.239

AC:

828

AN:

3478

EpiCase

AF:

0.175

EpiControl

AF:

0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.28

Sift

Benign

0.15

Sift4G

Benign

0.41

Polyphen

0.0090

Vest4

0.14

MPC

0.21

ClinPred

0.11

GERP RS

3.9

Varity_R

0.30

gMVP

0.48

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over