rs10521976

chrX-31678775-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004006.3(DMD):c.7872+600C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 111,365 control chromosomes in the GnomAD database, including 606 homozygotes. There are 3,816 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 0.12 (606 hom., 3816 hem., cov: 22)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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=-0.92).
• BP6: Variant X-31678775-G-A is Benign according to our data. Variant chrX-31678775-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.7872+600C>T		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.7872+600C>T		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.118 AC: 13089 AN: 111315 Hom.: 607 Cov.: 22 AF XY: 0.113 AC XY: 3802 AN XY: 33517

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0705

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.0524

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.118 AC: 13099 AN: 111365 Hom.: 606 Cov.: 22 AF XY: 0.114 AC XY: 3816 AN XY: 33577

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.0643

Gnomad4 EAS AF: 0.0519

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.125

Alfa AF: 0.117 Hom.: 4875

Bravo AF: 0.130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.17
Dann	Benign	0.80

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: rs10521976; hg19: chrX-31696892;