rs8103451

Positions:

• chr19-48970169-G-A
• chr19-48970169-G-T

Variant summary

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

The NM_002103.5(GYS1):​c.1810-314C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 479,504 control chromosomes in the GnomAD database, including 686 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 0.044 (216 hom., cov: 32)
  • Exomes 𝑓: 0.047 (470 hom.)
• Consequence: GYS1 NM_002103.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838

Genes affected

GYS1 (HGNC:4706): (glycogen synthase 1) The protein encoded by this gene catalyzes the addition of glucose monomers to the growing glycogen molecule through the formation of alpha-1,4-glycoside linkages. Mutations in this gene are associated with muscle glycogen storage disease. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYS1	NM_002103.5	c.1810-314C>T		intron_variant		ENST00000323798.8
GYS1	NM_001161587.2	c.1618-314C>T		intron_variant
GYS1	NR_027763.2	n.1825-314C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYS1	ENST00000323798.8	c.1810-314C>T		intron_variant		1	NM_002103.5	P1
GYS1	ENST00000263276.6	c.1618-314C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6748 AN: 151976 Hom.: 214 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0359

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0541

Gnomad OTH AF: 0.0392

GnomAD4 exome AF: 0.0466 AC: 15248 AN: 327410 Hom.: 470 AF XY: 0.0451 AC XY: 7799 AN XY: 173082

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.0624

Gnomad4 ASJ exome AF: 0.0246

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.0308

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.0520

Gnomad4 OTH exome AF: 0.0433

GnomAD4 genome AF: 0.0444 AC: 6756 AN: 152094 Hom.: 216 Cov.: 32 AF XY: 0.0479 AC XY: 3561 AN XY: 74344

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.0646

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0357

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0541

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0463 Hom.: 191

Bravo AF: 0.0383

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8103451; hg19: chr19-49473426;