3-49486803-T-G

Position:

• chr3-49486803-T-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+16370T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,096 control chromosomes in the GnomAD database, including 14,879 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 0.42 (14879 hom., cov: 33)
• Consequence: DAG1 NM_004393.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.98).
• 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+16370T>G		intron_variant		ENST00000308775.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAG1	ENST00000308775.7	c.-117+16370T>G		intron_variant		1	NM_004393.6	P1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63375 AN: 151978 Hom.: 14869 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.417 AC: 63402 AN: 152096 Hom.: 14879 Cov.: 33 AF XY: 0.423 AC XY: 31436 AN XY: 74360

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.426

Alfa AF: 0.416 Hom.: 5133

Bravo AF: 0.428

Asia WGS AF: 0.767 AC: 2659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.76
DANN	Benign	0.36

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: rs3924462; hg19: chr3-49524236;