3-49468840-A-AT

Position:

• chr3-49468840-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000469139(DAG1):​c.-332_-331insT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (28398 hom., cov: 0)
  • Exomes 𝑓: 0.33 (1 hom.)
• Consequence: DAG1 ENST00000469139 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0960

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-49468840-A-AT is Benign according to our data. Variant chr3-49468840-A-AT is described in ClinVar as [Benign]. Clinvar id is 1269929.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.49468840_49468841insT		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAG1	ENST00000469139	c.-332_-331insT		5_prime_UTR_variant	1/3	4		ENSP00000501165.2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 91011 AN: 146200 Hom.: 28387 Cov.: 0

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.667

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.333 AC: 10 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.400 AC XY: 8 AN XY: 20

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.622 AC: 91055 AN: 146282 Hom.: 28398 Cov.: 0 AF XY: 0.621 AC XY: 44089 AN XY: 71006

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.933

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.632

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

Nov 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs1553641460; hg19: chr3-49506273;