rs17121644

chr1-99919874-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000642.3(AGL):c.4482-1660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 152,234 control chromosomes in the GnomAD database, including 256 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 0.052 (256 hom., cov: 32)
• Consequence: AGL NM_000642.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652

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]

LOC124904230 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGL	NM_000642.3	c.4482-1660C>T		intron_variant		ENST00000361915.8
LOC124904230	XR_007066249.1	n.1145+4364G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGL	ENST00000361915.8	c.4482-1660C>T		intron_variant		1	NM_000642.3	P1

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7930 AN: 152116 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.0558

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.0446

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

GnomAD4 genome AF: 0.0521 AC: 7928 AN: 152234 Hom.: 256 Cov.: 32 AF XY: 0.0513 AC XY: 3818 AN XY: 74446

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.0302

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.0155

Gnomad4 SAS AF: 0.0454

Gnomad4 FIN AF: 0.0558

Gnomad4 NFE AF: 0.0457

Gnomad4 OTH AF: 0.0432

Alfa AF: 0.0414 Hom.: 156

Bravo AF: 0.0486

Asia WGS AF: 0.0280 AC: 97 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	1.2
Dann	Benign	0.47

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: rs17121644; hg19: chr1-100385430;