rs4625

Positions:

• chr3-49534707-A-G

Variant summary

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

The NM_004393.6(DAG1):​c.*1508A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,482 control chromosomes in the GnomAD database, including 7,259 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 0.30 (7207 hom., cov: 32)
  • Exomes 𝑓: 0.46 (52 hom.)
• Consequence: DAG1 NM_004393.6 3_prime_UTR
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.00600

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=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAG1	NM_004393.6	c.*1508A>G		3_prime_UTR_variant	3/3	ENST00000308775.7	NP_004384.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAG1	ENST00000308775.7	c.*1508A>G		3_prime_UTR_variant	3/3	1	NM_004393.6	ENSP00000312435	P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45168 AN: 151922 Hom.: 7201 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.457 AC: 201 AN: 440 Hom.: 52 Cov.: 0 AF XY: 0.455 AC XY: 120 AN XY: 264

Gnomad4 FIN exome AF: 0.456

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.297 AC: 45197 AN: 152042 Hom.: 7207 Cov.: 32 AF XY: 0.300 AC XY: 22260 AN XY: 74308

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.0593

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.295

Alfa AF: 0.302 Hom.: 14846

Bravo AF: 0.277

Asia WGS AF: 0.148 AC: 522 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4625; hg19: chr3-49572140;