19-48970770-A-T

Position:

• chr19-48970770-A-T

Variant summary

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

The ENST00000323798.8(GYS1):​c.1646-61T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,534,400 control chromosomes in the GnomAD database, including 112,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11944 hom., cov: 30)
  • Exomes 𝑓: 0.38 (100753 hom.)
• Consequence: GYS1 ENST00000323798.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0610

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 19-48970770-A-T is Benign according to our data. Variant chr19-48970770-A-T is described in ClinVar as [Benign]. Clinvar id is 676132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYS1	NM_002103.5	c.1646-61T>A		intron_variant		ENST00000323798.8	NP_002094.2
GYS1	NM_001161587.2	c.1454-61T>A		intron_variant			NP_001155059.1
GYS1	NR_027763.2	n.1661-61T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYS1	ENST00000323798.8	c.1646-61T>A		intron_variant		1	NM_002103.5	ENSP00000317904	P1
GYS1	ENST00000263276.6	c.1454-61T>A		intron_variant		1		ENSP00000263276
GYS1	ENST00000472004.5	n.558T>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59799 AN: 151462 Hom.: 11926 Cov.: 30

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.380 AC: 525635 AN: 1382820 Hom.: 100753 Cov.: 22 AF XY: 0.380 AC XY: 262614 AN XY: 691684

Gnomad4 AFR exome AF: 0.455

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.463

Gnomad4 EAS exome AF: 0.384

Gnomad4 SAS exome AF: 0.324

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.384

GnomAD4 genome AF: 0.395 AC: 59862 AN: 151580 Hom.: 11944 Cov.: 30 AF XY: 0.390 AC XY: 28904 AN XY: 74056

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.402

Alfa AF: 0.386 Hom.: 1359

Bravo AF: 0.397

Asia WGS AF: 0.301 AC: 1049 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.8
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2270938; hg19: chr19-49474027; COSMIC: COSV54402994; COSMIC: COSV54402994;