rs10521971

chrX-31480683-T-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.8548-1580A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 109,269 control chromosomes in the GnomAD database, including 110 homozygotes. There are 895 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 0.031 (110 hom., 895 hem., cov: 22)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49

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=-0.8).
• BP6: Variant X-31480683-T-C is Benign according to our data. Variant chrX-31480683-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.8548-1580A>G		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.8548-1580A>G		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 3382 AN: 109220 Hom.: 110 Cov.: 22 AF XY: 0.0281 AC XY: 885 AN XY: 31546

Gnomad AFR AF: 0.0790

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0437

Gnomad SAS AF: 0.00722

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.0212

Gnomad NFE AF: 0.00917

Gnomad OTH AF: 0.0275

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

GnomAD4 genome AF: 0.0311 AC: 3393 AN: 109269 Hom.: 110 Cov.: 22 AF XY: 0.0283 AC XY: 895 AN XY: 31605

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.0433

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.00917

Gnomad4 OTH AF: 0.0264

Alfa AF: 0.0277 Hom.: 147

Bravo AF: 0.0357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.3
Dann	Benign	0.80

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: rs10521971; hg19: chrX-31498800;