chr3-49483525-A-G

Position:

• chr3-49483525-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.-117+13092A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,738 control chromosomes in the GnomAD database, including 16,606 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 0.45 (16606 hom., cov: 31)
• Consequence: DAG1 NM_004393.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAG1	NM_004393.6	c.-117+13092A>G		intron_variant		ENST00000308775.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAG1	ENST00000308775.7	c.-117+13092A>G		intron_variant		1	NM_004393.6	P1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68335 AN: 151622 Hom.: 16593 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.451 AC: 68382 AN: 151738 Hom.: 16606 Cov.: 31 AF XY: 0.456 AC XY: 33799 AN XY: 74148

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.448

Alfa AF: 0.435 Hom.: 3429

Bravo AF: 0.466

Asia WGS AF: 0.779 AC: 2701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.60

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: rs1568661; hg19: chr3-49520958;