X-32378707-G-T

Variant names:

• chrX-32378707-G-T
• rs2207796
• NM_004006.3:c.4845+1803C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004006.3(DMD):​c.4845+1803C>A 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 0.68 (18555 hom., 21726 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• Publications: 1 publications found

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]

DMD Gene-Disease associations (from GenCC):

• Becker muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• dilated cardiomyopathy 3B

  Inheritance: XL Classification: DEFINITIVE Submitted by: Ambry Genetics
• Duchenne and Becker muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• Duchenne muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• progressive muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3	c.4845+1803C>A		intron_variant	Intron 34 of 78	ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.4845+1803C>A		intron_variant	Intron 34 of 78	1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes AF: 0.682 AC: 74599 AN: 109361 Hom.: 18554 Cov.: 22

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.552

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.673

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: 0.682 AC: 74626 AN: 109405 Hom.: 18555 Cov.: 22 AF XY: 0.682 AC XY: 21726 AN XY: 31875

African (AFR) AF: 0.836 AC: 25381 AN: 30362

American (AMR) AF: 0.749 AC: 7624 AN: 10178

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1333 AN: 2612

East Asian (EAS) AF: 0.758 AC: 2650 AN: 3495

South Asian (SAS) AF: 0.713 AC: 1866 AN: 2617

European-Finnish (FIN) AF: 0.654 AC: 3583 AN: 5478

Middle Eastern (MID) AF: 0.550 AC: 116 AN: 211

European-Non Finnish (NFE) AF: 0.589 AC: 30804 AN: 52307

Other (OTH) AF: 0.666 AC: 982 AN: 1475

Alfa AF: 0.654 Hom.: 5156

Bravo AF: 0.700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.77
DANN	Benign	0.24
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2207796; hg19: chrX-32396824;