rs1456737

Positions:

• chrX-32207138-A-C
• chrX-32207138-A-T

Variant summary

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

The NM_004006.3(DMD):​c.6438+9778T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 110,518 control chromosomes in the GnomAD database, including 8,676 homozygotes. There are 15,189 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 0.46 (8676 hom., 15189 hem., cov: 22)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.6438+9778T>G		intron_variant		ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.6438+9778T>G		intron_variant		1	NM_004006.3	ENSP00000354923	P4

Frequencies

GnomAD3 genomes AF: 0.461 AC: 50977 AN: 110470 Hom.: 8678 Cov.: 22 AF XY: 0.463 AC XY: 15162 AN XY: 32730

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.462 AC: 51005 AN: 110518 Hom.: 8676 Cov.: 22 AF XY: 0.463 AC XY: 15189 AN XY: 32788

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.483

Alfa AF: 0.472 Hom.: 27259

Bravo AF: 0.471

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.49
DANN	Benign	0.59

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: rs1456737; hg19: chrX-32225255;