rs2274570

chr1-99910892-G-Achr1-99910892-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000642.3(AGL):c.3836+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 1,582,054 control chromosomes in the GnomAD database, including 199,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16725 hom., cov: 31)
  • Exomes 𝑓: 0.50 (183175 hom.)
• Consequence: AGL NM_000642.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.294

Genes affected

AGL (HGNC:321): (amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase) This gene encodes the glycogen debrancher enzyme which is involved in glycogen degradation. This enzyme has two independent catalytic activities which occur at different sites on the protein: a 4-alpha-glucotransferase activity and a amylo-1,6-glucosidase activity. Mutations in this gene are associated with glycogen storage disease although a wide range of enzymatic and clinical variability occurs which may be due to tissue-specific alternative splicing. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-99910892-G-A is Benign according to our data. Variant chr1-99910892-G-A is described in ClinVar as [Benign]. Clinvar id is 256744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGL	NM_000642.3	c.3836+45G>A		intron_variant		ENST00000361915.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGL	ENST00000361915.8	c.3836+45G>A		intron_variant		1	NM_000642.3	P1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70337 AN: 151300 Hom.: 16702 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.470

GnomAD3 exomes AF: 0.482 AC: 115140 AN: 238790 Hom.: 28086 AF XY: 0.474 AC XY: 61067 AN XY: 128934

Gnomad AFR exome AF: 0.371

Gnomad AMR exome AF: 0.571

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.543

Gnomad SAS exome AF: 0.365

Gnomad FIN exome AF: 0.493

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.478

GnomAD4 exome AF: 0.502 AC: 718768 AN: 1430636 Hom.: 183175 Cov.: 26 AF XY: 0.497 AC XY: 354033 AN XY: 712122

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.565

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.612

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.502

Gnomad4 NFE exome AF: 0.515

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.465 AC: 70402 AN: 151418 Hom.: 16725 Cov.: 31 AF XY: 0.463 AC XY: 34233 AN XY: 73966

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.475

Alfa AF: 0.493 Hom.: 32419

Bravo AF: 0.468

Asia WGS AF: 0.477 AC: 1661 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Glycogen storage disease type III Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.65
Dann	Benign	0.20

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: rs2274570; hg19: chr1-100376448; COSMIC: COSV54050212;