Variant rs2274570 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.294

Variant links:

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]

AGL links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.3836+45G>A		intron_variant		ENST00000361915.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGL	ENST00000361915.8 linkuse as main transcript	c.3836+45G>A		intron_variant		1	NM_000642.3	P1	P35573-1

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70337

AN:

151300

Hom.:

16702

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.497

AC XY:

354033

AN XY:

712122

show subpopulations

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.:

AF XY:

0.463

AC XY:

34233

AN XY:

73966

show subpopulations

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over