rs6527185

Positions:

• chrX-32346651-C-T

Variant summary

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

The NM_004006.3(DMD):​c.5449-571G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 110,464 control chromosomes in the GnomAD database, including 2,635 homozygotes. There are 6,604 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 0.22 (2635 hom., 6604 hem., cov: 23)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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]

DMD (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.5449-571G>A		intron_variant		ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.5449-571G>A		intron_variant		1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 23762 AN: 110414 Hom.: 2636 Cov.: 23 AF XY: 0.202 AC XY: 6602 AN XY: 32746

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.0365

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0977

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.215 AC: 23762 AN: 110464 Hom.: 2635 Cov.: 23 AF XY: 0.201 AC XY: 6604 AN XY: 32806

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0980

Gnomad4 SAS AF: 0.0457

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.201

Alfa AF: 0.191 Hom.: 1233

Bravo AF: 0.229

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.018
DANN	Benign	0.55

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: rs6527185; hg19: chrX-32364768;