rs10521977

Positions:

• chrX-31731346-G-A
• chrX-31731346-G-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.7543-1598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 110,508 control chromosomes in the GnomAD database, including 11,289 homozygotes. There are 16,094 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 0.51 (11289 hom., 16094 hem., cov: 23)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-31731346-G-A is Benign according to our data. Variant chrX-31731346-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.7543-1598C>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.7543-1598C>T		intron_variant		1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes AF: 0.509 AC: 56197 AN: 110453 Hom.: 11280 Cov.: 23 AF XY: 0.490 AC XY: 16046 AN XY: 32771

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.509 AC: 56254 AN: 110508 Hom.: 11289 Cov.: 23 AF XY: 0.490 AC XY: 16094 AN XY: 32836

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.520

Alfa AF: 0.317 Hom.: 2096

Bravo AF: 0.535

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.6
DANN	Benign	0.33

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: rs10521977; hg19: chrX-31749463;