X-32378707-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004006.3(DMD):c.4845+1803C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (18555 hom., 21726 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

Genes affected

DMD (HGNC:2928): (dystrophin) This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BS2: High Homozygotes in GnomAd at 18554 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.4845+1803C>A		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.4845+1803C>A		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.682 AC: 74599 AN: 109361 Hom.: 18554 Cov.: 22 AF XY: 0.682 AC XY: 21690 AN XY: 31821

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.552

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.673

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.682 AC: 74626 AN: 109405 Hom.: 18555 Cov.: 22 AF XY: 0.682 AC XY: 21726 AN XY: 31875

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.666

Alfa AF: 0.654 Hom.: 5156

Bravo AF: 0.700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.77
Dann	Benign	0.24

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: rs2207796; hg19: chrX-32396824;