rs1921961

chrX-31578850-C-T

Variant summary

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

The NM_004006.3(DMD):c.8217+48823G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 111,232 control chromosomes in the GnomAD database, including 4,377 homozygotes. There are 10,358 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 0.32 (4377 hom., 10358 hem., cov: 23)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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-31578850-C-T is Benign according to our data. Variant chrX-31578850-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.8217+48823G>A		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.8217+48823G>A		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.323 AC: 35914 AN: 111179 Hom.: 4373 Cov.: 23 AF XY: 0.308 AC XY: 10306 AN XY: 33413

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.323 AC: 35975 AN: 111232 Hom.: 4377 Cov.: 23 AF XY: 0.309 AC XY: 10358 AN XY: 33476

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.361

Alfa AF: 0.308 Hom.: 2164

Bravo AF: 0.346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.64
Dann	Benign	0.65

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: rs1921961; hg19: chrX-31596967;