rs10522021

Positions:

• chrX-33236794-C-G

Variant summary

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

The ENST00000288447.9(DMD):​c.7+102465G>C 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 111,069 control chromosomes in the GnomAD database, including 1,223 homozygotes. There are 3,746 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 0.12 (1223 hom., 3746 hem., cov: 21)
• Consequence: DMD ENST00000288447.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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=-0.91).
• BP6: Variant X-33236794-C-G is Benign according to our data. Variant chrX-33236794-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_000109.4	c.7+102465G>C		intron_variant
DMD	XM_006724469.4	c.7+102465G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000288447.9	c.7+102465G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 13449 AN: 111020 Hom.: 1220 Cov.: 21 AF XY: 0.112 AC XY: 3726 AN XY: 33266

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0750

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.0644

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.0965

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.0434

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.121 AC: 13475 AN: 111069 Hom.: 1223 Cov.: 21 AF XY: 0.112 AC XY: 3746 AN XY: 33325

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.0649

Gnomad4 ASJ AF: 0.0644

Gnomad4 EAS AF: 0.0208

Gnomad4 SAS AF: 0.0965

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.0433

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0871 Hom.: 476

Bravo AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10522021; hg19: chrX-33254911;