3-49488529-G-T

Position:

• chr3-49488529-G-T

Variant summary

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

The NM_004393.6(DAG1):​c.-117+18096G>T 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 152,030 control chromosomes in the GnomAD database, including 14,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14890 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: DAG1 NM_004393.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.59

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]

DAG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-49488529-G-T is Benign according to our data. Variant chr3-49488529-G-T is described in ClinVar as [Benign]. Clinvar id is 1292613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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	Protein	UniProt
DAG1	NM_004393.6	c.-117+18096G>T		intron_variant		ENST00000308775.7	NP_004384.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAG1	ENST00000308775.7	c.-117+18096G>T		intron_variant		1	NM_004393.6	ENSP00000312435.2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63377 AN: 151912 Hom.: 14880 Cov.: 32

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: 0.681

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.417 AC: 63404 AN: 152026 Hom.: 14890 Cov.: 32 AF XY: 0.423 AC XY: 31431 AN XY: 74298

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.426

Alfa AF: 0.423 Hom.: 1756

Bravo AF: 0.428

Asia WGS AF: 0.767 AC: 2659 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.032
DANN	Benign	0.41

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: rs4855861; hg19: chr3-49525962;