3-49470414-G-A

Position:

• chr3-49470414-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_004393.6(DAG1):​c.-136G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,058 control chromosomes in the GnomAD database, including 15,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15805 hom., cov: 33)
  • Exomes 𝑓: 0.51 (16 hom.)
• Consequence: DAG1 NM_004393.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0430

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 3-49470414-G-A is Benign according to our data. Variant chr3-49470414-G-A is described in ClinVar as [Benign]. Clinvar id is 380775.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.-136G>A		5_prime_UTR_variant	1/3	ENST00000308775.7	NP_004384.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAG1	ENST00000308775	c.-136G>A		5_prime_UTR_variant	1/3	1	NM_004393.6	ENSP00000312435.2

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66326 AN: 151810 Hom.: 15796 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.435

GnomAD4 exome AF: 0.507 AC: 70 AN: 138 Hom.: 16 Cov.: 0 AF XY: 0.517 AC XY: 60 AN XY: 116

Gnomad4 AFR exome AF: 0.333

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.525

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.437 AC: 66364 AN: 151920 Hom.: 15805 Cov.: 33 AF XY: 0.443 AC XY: 32871 AN XY: 74266

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.440

Alfa AF: 0.434 Hom.: 10742

Bravo AF: 0.451

Asia WGS AF: 0.775 AC: 2669 AN: 3452

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 26, 2016

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4855839; hg19: chr3-49507847;