rs6653586

Positions:

• chrX-32621263-G-A

Variant summary

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

The NM_004006.3(DMD):​c.1332-6810C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 111,070 control chromosomes in the GnomAD database, including 139 homozygotes. There are 1,323 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 0.045 (139 hom., 1323 hem., cov: 22)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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=-0.9).
• BP6: Variant X-32621263-G-A is Benign according to our data. Variant chrX-32621263-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.1332-6810C>T		intron_variant		ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.1332-6810C>T		intron_variant		1	NM_004006.3	ENSP00000354923	P4

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 5020 AN: 111021 Hom.: 139 Cov.: 22 AF XY: 0.0396 AC XY: 1315 AN XY: 33233

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00586

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.0368

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.0346

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0561

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

GnomAD4 genome AF: 0.0453 AC: 5032 AN: 111070 Hom.: 139 Cov.: 22 AF XY: 0.0397 AC XY: 1323 AN XY: 33292

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0271

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.0518

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.0116

Gnomad4 NFE AF: 0.0206

Gnomad4 OTH AF: 0.0554

Alfa AF: 0.0315 Hom.: 143

Bravo AF: 0.0498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.63

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: rs6653586; hg19: chrX-32639380;