rs5972556

chrX-32394097-G-AchrX-32394097-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004006.3(DMD):c.4234-3916C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.56 (12289 hom., 18501 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High Homozygotes in GnomAd at 12293 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.4234-3916C>T		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.4234-3916C>T		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.561 AC: 61924 AN: 110409 Hom.: 12293 Cov.: 23 AF XY: 0.565 AC XY: 18467 AN XY: 32705

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.573

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.561 AC: 61944 AN: 110459 Hom.: 12289 Cov.: 23 AF XY: 0.565 AC XY: 18501 AN XY: 32765

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.569

Alfa AF: 0.527 Hom.: 51991

Bravo AF: 0.573

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.2
Dann	Benign	0.19

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: rs5972556; hg19: chrX-32412214;