rs2748314

Positions:

• chrX-32755366-G-A
• chrX-32755366-G-C
• chrX-32755366-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004006.3(DMD):​c.649+54127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 109,743 control chromosomes in the GnomAD database, including 6,611 homozygotes. There are 11,268 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (6611 hom., 11268 hem., cov: 22)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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-AS3 (HGNC:40185): (DMD antisense RNA 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.649+54127C>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.649+54127C>T		intron_variant		1	NM_004006.3	ENSP00000354923	P4
DMD-AS3	ENST00000439592.1	n.50+377G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.369 AC: 40485 AN: 109693 Hom.: 6612 Cov.: 22 AF XY: 0.351 AC XY: 11234 AN XY: 32031

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.369 AC: 40514 AN: 109743 Hom.: 6611 Cov.: 22 AF XY: 0.351 AC XY: 11268 AN XY: 32091

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.385

Alfa AF: 0.260 Hom.: 11752

Bravo AF: 0.390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.47
DANN	Benign	0.56

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: rs2748314; hg19: chrX-32773483;