rs10522018

Positions:

• chrX-32975029-T-G

Variant summary

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

The NM_004006.3(DMD):​c.93+45110A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 111,837 control chromosomes in the GnomAD database, including 237 homozygotes. There are 1,865 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 0.059 (237 hom., 1865 hem., cov: 23)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502

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=-0.62).
• BP6: Variant X-32975029-T-G is Benign according to our data. Variant chrX-32975029-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.93+45110A>C		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.93+45110A>C		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 6604 AN: 111785 Hom.: 239 Cov.: 23 AF XY: 0.0545 AC XY: 1852 AN XY: 34009

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.0183

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0168

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0508

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

GnomAD4 genome AF: 0.0591 AC: 6615 AN: 111837 Hom.: 237 Cov.: 23 AF XY: 0.0547 AC XY: 1865 AN XY: 34071

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0677

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.0183

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.0293

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0373 Hom.: 1956

Bravo AF: 0.0702

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.86

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: rs10522018; hg19: chrX-32993146;