rs716354

Positions:

• chrX-31615975-G-A
• chrX-31615975-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.8217+11698C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 110,892 control chromosomes in the GnomAD database, including 5,973 homozygotes. There are 11,507 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 0.36 (5973 hom., 11507 hem., cov: 23)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

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=-1.0).
• BP6: Variant X-31615975-G-A is Benign according to our data. Variant chrX-31615975-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.8217+11698C>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.8217+11698C>T		intron_variant		1	NM_004006.3	ENSP00000354923	P4

Frequencies

GnomAD3 genomes AF: 0.364 AC: 40346 AN: 110836 Hom.: 5968 Cov.: 23 AF XY: 0.346 AC XY: 11459 AN XY: 33098

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.364 AC: 40400 AN: 110892 Hom.: 5973 Cov.: 23 AF XY: 0.347 AC XY: 11507 AN XY: 33164

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.389

Alfa AF: 0.301 Hom.: 25453

Bravo AF: 0.391

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.57

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: rs716354; hg19: chrX-31634092;