rs10521979

chrX-31769502-A-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004006.3(DMD):c.7542+4458T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 111,622 control chromosomes in the GnomAD database, including 698 homozygotes. There are 4,421 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.13 (698 hom., 4421 hem., cov: 23)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-31769502-A-C is Benign according to our data. Variant chrX-31769502-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.7542+4458T>G		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.7542+4458T>G		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.131 AC: 14583 AN: 111570 Hom.: 700 Cov.: 23 AF XY: 0.131 AC XY: 4413 AN XY: 33772

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.0423

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.151

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.131 AC: 14583 AN: 111622 Hom.: 698 Cov.: 23 AF XY: 0.131 AC XY: 4421 AN XY: 33834

Gnomad4 AFR AF: 0.0893

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.147

Alfa AF: 0.138 Hom.: 2697

Bravo AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	10
Dann	Benign	0.79

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: rs10521979; hg19: chrX-31787619;