rs16990134

Positions:

• chrX-32168051-A-G

Variant summary

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

The NM_004006.3(DMD):​c.6438+48865T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 112,259 control chromosomes in the GnomAD database, including 413 homozygotes. There are 2,676 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 0.086 (413 hom., 2676 hem., cov: 23)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.6438+48865T>C		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.6438+48865T>C		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.0862 AC: 9677 AN: 112205 Hom.: 411 Cov.: 23 AF XY: 0.0777 AC XY: 2674 AN XY: 34407

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0498

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.000834

Gnomad SAS AF: 0.0577

Gnomad FIN AF: 0.0413

Gnomad MID AF: 0.0628

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.0638

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

GnomAD4 genome AF: 0.0862 AC: 9679 AN: 112259 Hom.: 413 Cov.: 23 AF XY: 0.0776 AC XY: 2676 AN XY: 34471

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0404

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.000837

Gnomad4 SAS AF: 0.0572

Gnomad4 FIN AF: 0.0413

Gnomad4 NFE AF: 0.0681

Gnomad4 OTH AF: 0.0617

Alfa AF: 0.0863 Hom.: 554

Bravo AF: 0.0884

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.40

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: rs16990134; hg19: chrX-32186168;