rs1456729

chrX-32269126-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004006.3(DMD):c.6290+18403A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 110,418 control chromosomes in the GnomAD database, including 814 homozygotes. There are 3,837 hemizygotes in GnomAD. 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 0.12 (814 hom., 3837 hem., cov: 22)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.6290+18403A>G		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.6290+18403A>G		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 13381 AN: 110363 Hom.: 816 Cov.: 22 AF XY: 0.118 AC XY: 3838 AN XY: 32601

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.121 AC: 13373 AN: 110418 Hom.: 814 Cov.: 22 AF XY: 0.117 AC XY: 3837 AN XY: 32666

Gnomad4 AFR AF: 0.0262

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0121

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.114

Alfa AF: 0.136 Hom.: 1152

Bravo AF: 0.116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.1
Dann	Benign	0.62

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: rs1456729; hg19: chrX-32287243;