20-25259553-G-T

Variant names:

• chr20-25259553-G-T
• rs2281558
• NM_002862.4:c.345+215G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002862.4(PYGB):​c.345+215G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,104 control chromosomes in the GnomAD database, including 4,568 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.

• Frequency: Genomes: 𝑓 0.23 (4568 hom., cov: 32)
• Consequence: PYGB NM_002862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 21 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGB	NM_002862.4	c.345+215G>T		intron_variant	Intron 2 of 19	ENST00000216962.9	NP_002853.2
PYGB	XM_047440342.1	c.345+215G>T		intron_variant	Intron 2 of 15		XP_047296298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYGB	ENST00000216962.9	c.345+215G>T		intron_variant	Intron 2 of 19	1	NM_002862.4	ENSP00000216962.3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35242 AN: 151986 Hom.: 4567 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.230

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.232 AC: 35247 AN: 152104 Hom.: 4568 Cov.: 32 AF XY: 0.236 AC XY: 17510 AN XY: 74328

African (AFR) AF: 0.158 AC: 6571 AN: 41506

American (AMR) AF: 0.191 AC: 2927 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3470

East Asian (EAS) AF: 0.583 AC: 3002 AN: 5148

South Asian (SAS) AF: 0.319 AC: 1537 AN: 4820

European-Finnish (FIN) AF: 0.259 AC: 2746 AN: 10582

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16913 AN: 67970

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.230 Hom.: 5506

Bravo AF: 0.225

Asia WGS AF: 0.395 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.61
DANN	Benign	0.59
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2281558; hg19: chr20-25240189;