chr3-49534707-A-G

Variant names:

• chr3-49534707-A-G
• rs4625
• NM_004393.6:c.*1508A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004393.6(DAG1):​c.*1508A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,482 control chromosomes in the GnomAD database, including 7,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.30 (7207 hom., cov: 32)
  • Exomes 𝑓: 0.46 (52 hom.)
• Consequence: DAG1 NM_004393.6 3_prime_UTR
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.00600
• Publications: 61 publications found

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]

BSN-DT (HGNC:42445): (BSN divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004393.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAG1	NM_004393.6	MANE Select	c.*1508A>G		3_prime_UTR	Exon 3 of 3	NP_004384.5
	DAG1	NM_001165928.4		c.*1508A>G		3_prime_UTR	Exon 6 of 6	NP_001159400.3
	DAG1	NM_001177634.3		c.*1508A>G		3_prime_UTR	Exon 6 of 6	NP_001171105.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAG1	ENST00000308775.7	TSL:1 MANE Select	c.*1508A>G		3_prime_UTR	Exon 3 of 3	ENSP00000312435.2
	BSN-DT	ENST00000816618.1		n.883T>C		non_coding_transcript_exon	Exon 6 of 6
	BSN-DT	ENST00000816619.1		n.450T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45168 AN: 151922 Hom.: 7201 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.457 AC: 201 AN: 440 Hom.: 52 Cov.: 0 AF XY: 0.455 AC XY: 120 AN XY: 264

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.456 AC: 195 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AF: 0.500 AC: 4 AN: 8

GnomAD4 genome AF: 0.297 AC: 45197 AN: 152042 Hom.: 7207 Cov.: 32 AF XY: 0.300 AC XY: 22260 AN XY: 74308

African (AFR) AF: 0.294 AC: 12189 AN: 41446

American (AMR) AF: 0.219 AC: 3342 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1605 AN: 3472

East Asian (EAS) AF: 0.0593 AC: 307 AN: 5180

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4826

European-Finnish (FIN) AF: 0.474 AC: 5000 AN: 10540

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20767 AN: 67972

Other (OTH) AF: 0.295 AC: 624 AN: 2114

Alfa AF: 0.299 Hom.: 24070

Bravo AF: 0.277

Asia WGS AF: 0.148 AC: 522 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

May 13, 2011

Leiden Muscular Dystrophy (DAG1)

Significance: not provided

Review Status: no classification provided

Collection Method: curation

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		0.0060
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4625; hg19: chr3-49572140;