3-49510128-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004393.6(DAG1):c.-116-291T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 407,426 control chromosomes in the GnomAD database, including 18,826 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6518 hom., cov: 33)
  • Exomes 𝑓: 0.29 (12308 hom.)
• Consequence: DAG1 NM_004393.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.168

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-49510128-T-C is Benign according to our data. Variant chr3-49510128-T-C is described in ClinVar as [Benign]. Clinvar id is 668114.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAG1	NM_004393.6	c.-116-291T>C		intron_variant		ENST00000308775.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAG1	ENST00000308775.7	c.-116-291T>C		intron_variant		1	NM_004393.6	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42596 AN: 152040 Hom.: 6516 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.290 AC: 74050 AN: 255268 Hom.: 12308 AF XY: 0.288 AC XY: 37863 AN XY: 131280

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.449

Gnomad4 EAS exome AF: 0.0641

Gnomad4 SAS exome AF: 0.238

Gnomad4 FIN exome AF: 0.446

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.280 AC: 42611 AN: 152158 Hom.: 6518 Cov.: 33 AF XY: 0.283 AC XY: 21062 AN XY: 74376

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.0589

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.286

Alfa AF: 0.277 Hom.: 895

Bravo AF: 0.258

Asia WGS AF: 0.142 AC: 500 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.6
Dann	Benign	0.62

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: rs7622302; hg19: chr3-49547561;