chr3-49487345-G-C

Position:

• chr3-49487345-G-C

Variant summary

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

The NM_001165928.4(DAG1):​c.-386G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,236 control chromosomes in the GnomAD database, including 3,370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3368 hom., cov: 32)
  • Exomes 𝑓: 0.38 (2 hom.)
• Consequence: DAG1 NM_001165928.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.04

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=-0.87).
• BP6: Variant 3-49487345-G-C is Benign according to our data. Variant chr3-49487345-G-C is described in ClinVar as [Benign]. Clinvar id is 1179379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAG1	NM_004393.6	c.-117+16912G>C		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+16912G>C		intron_variant		1	NM_004393.6	ENSP00000312435.2

Frequencies

GnomAD3 genomes AF: 0.197 AC: 30013 AN: 152084 Hom.: 3366 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.00864

Gnomad SAS AF: 0.0849

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.382 AC: 13 AN: 34 Hom.: 2 Cov.: 0 AF XY: 0.417 AC XY: 10 AN XY: 24

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.367

GnomAD4 genome AF: 0.197 AC: 30025 AN: 152202 Hom.: 3368 Cov.: 32 AF XY: 0.191 AC XY: 14188 AN XY: 74410

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.00847

Gnomad4 SAS AF: 0.0850

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.220

Alfa AF: 0.225 Hom.: 512

Bravo AF: 0.194

Asia WGS AF: 0.0550 AC: 193 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	Oct 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.61

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: rs6783003; hg19: chr3-49524778;