rs12583

chr3-49534029-G-T

Variant summary

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

The NM_004393.6(DAG1):c.*830G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,586 control chromosomes in the GnomAD database, including 4,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.24 (4604 hom., cov: 33)
  • Exomes 𝑓: 0.24 (14 hom.)
• Consequence: DAG1 NM_004393.6 3_prime_UTR
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.10

Genes affected

DAG1 (HGNC:2666): (dystroglycan 1) This gene encodes dystroglycan, a central component of dystrophin-glycoprotein complex that links the extracellular matrix and the cytoskeleton in the skeletal muscle. The encoded preproprotein undergoes O- and N-glycosylation, and proteolytic processing to generate alpha and beta subunits. Certain mutations in this gene are known to cause distinct forms of muscular dystrophy. Alternative splicing results in multiple transcript variants, all encoding the same protein. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAG1	NM_004393.6	c.*830G>T		3_prime_UTR_variant	3/3	ENST00000308775.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAG1	ENST00000308775.7	c.*830G>T		3_prime_UTR_variant	3/3	1	NM_004393.6	P1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36121 AN: 151976 Hom.: 4591 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.00866

Gnomad SAS AF: 0.0863

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.236 AC: 116 AN: 492 Hom.: 14 Cov.: 0 AF XY: 0.268 AC XY: 81 AN XY: 302

Gnomad4 AMR exome AF: 0.143

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.238 AC: 36165 AN: 152094 Hom.: 4604 Cov.: 33 AF XY: 0.230 AC XY: 17087 AN XY: 74352

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.00849

Gnomad4 SAS AF: 0.0863

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.246

Alfa AF: 0.254 Hom.: 804

Bravo AF: 0.240

Asia WGS AF: 0.0670 AC: 234 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

curation

Leiden Muscular Dystrophy (DAG1)

May 13, 2011

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	14
Dann	Benign	0.80

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: rs12583; hg19: chr3-49571462;