3-49488867-C-T

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.-117+18434C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,398 control chromosomes in the GnomAD database, including 14,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14865 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DAG1 NM_004393.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.934

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=-1.0).
• BP6: Variant 3-49488867-C-T is Benign according to our data. Variant chr3-49488867-C-T is described in ClinVar as [Benign]. Clinvar id is 1251824.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
DAG1	NM_004393.6	c.-117+18434C>T		intron_variant		ENST00000308775.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAG1	ENST00000308775.7	c.-117+18434C>T		intron_variant		1	NM_004393.6	P1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63270 AN: 151278 Hom.: 14855 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.421

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.418 AC: 63298 AN: 151398 Hom.: 14865 Cov.: 31 AF XY: 0.424 AC XY: 31369 AN XY: 73958

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.427

Alfa AF: 0.417 Hom.: 2186

Bravo AF: 0.428

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

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.21
Dann	Benign	0.49

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: rs4855859; hg19: chr3-49526300;