X-31672862-C-T

Position:

• chrX-31672862-C-T

Variant summary

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

The NM_004006.3(DMD):​c.7872+6513G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 110,822 control chromosomes in the GnomAD database, including 7,484 homozygotes. There are 12,744 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 0.41 (7484 hom., 12744 hem., cov: 23)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.7872+6513G>A		intron_variant		ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.7872+6513G>A		intron_variant		1	NM_004006.3	ENSP00000354923	P4

Frequencies

GnomAD3 genomes AF: 0.406 AC: 44926 AN: 110764 Hom.: 7476 Cov.: 23 AF XY: 0.385 AC XY: 12699 AN XY: 33026

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.413

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.406 AC: 44980 AN: 110822 Hom.: 7484 Cov.: 23 AF XY: 0.385 AC XY: 12744 AN XY: 33092

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.433

Alfa AF: 0.342 Hom.: 7831

Bravo AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.22
DANN	Benign	0.53

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: rs5971587; hg19: chrX-31690979;