rs6138553

Variant names:

• chr20-25258597-G-A
• rs6138553
• NM_002862.4:c.244-640G>A

Variant summary

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

The NM_002862.4(PYGB):​c.244-640G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,164 control chromosomes in the GnomAD database, including 13,069 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 0.39 (13069 hom., cov: 33)
• Consequence: PYGB NM_002862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• Publications: 11 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 = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGB	NM_002862.4	c.244-640G>A		intron_variant	Intron 1 of 19	ENST00000216962.9	NP_002853.2
PYGB	XM_047440342.1	c.244-640G>A		intron_variant	Intron 1 of 15		XP_047296298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYGB	ENST00000216962.9	c.244-640G>A		intron_variant	Intron 1 of 19	1	NM_002862.4	ENSP00000216962.3

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59503 AN: 152046 Hom.: 13070 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.391 AC: 59512 AN: 152164 Hom.: 13069 Cov.: 33 AF XY: 0.395 AC XY: 29413 AN XY: 74382

African (AFR) AF: 0.240 AC: 9966 AN: 41534

American (AMR) AF: 0.355 AC: 5426 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1102 AN: 3472

East Asian (EAS) AF: 0.919 AC: 4760 AN: 5182

South Asian (SAS) AF: 0.444 AC: 2139 AN: 4822

European-Finnish (FIN) AF: 0.454 AC: 4790 AN: 10562

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29937 AN: 67976

Other (OTH) AF: 0.381 AC: 804 AN: 2110

Alfa AF: 0.398 Hom.: 5598

Bravo AF: 0.378

Asia WGS AF: 0.651 AC: 2263 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	0.68
DANN	Benign	0.52
PhyloP100		-0.55
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: rs6138553; hg19: chr20-25239233;