3-49488611-A-T

Position:

• chr3-49488611-A-T

Variant summary

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

The NM_004393.6(DAG1):​c.-117+18178A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 150,356 control chromosomes in the GnomAD database, including 61,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.90 (61278 hom., cov: 29)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: DAG1 NM_004393.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.944

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=-1.02).
• BP6: Variant 3-49488611-A-T is Benign according to our data. Variant chr3-49488611-A-T is described in ClinVar as [Benign]. Clinvar id is 1252410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAG1	NM_004393.6	c.-117+18178A>T		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+18178A>T		intron_variant		1	NM_004393.6	ENSP00000312435.2

Frequencies

GnomAD3 genomes AF: 0.903 AC: 135665 AN: 150262 Hom.: 61236 Cov.: 29

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.915

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.969

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.919

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.912

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.903 AC: 135753 AN: 150354 Hom.: 61278 Cov.: 29 AF XY: 0.902 AC XY: 66139 AN XY: 73294

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.927

Gnomad4 ASJ AF: 0.861

Gnomad4 EAS AF: 0.982

Gnomad4 SAS AF: 0.968

Gnomad4 FIN AF: 0.865

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.913

Alfa AF: 0.295 Hom.: 895

Bravo AF: 0.908

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	Jul 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs4855860; hg19: chr3-49526044;