X-31672862-C-T

Variant names:

• chrX-31672862-C-T
• rs5971587
• NM_004006.3:c.7872+6513G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004006.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMD	NM_004006.3	MANE Select	c.7872+6513G>A		intron	N/A	NP_003997.2	P11532-1
	DMD	NM_004009.3		c.7860+6513G>A		intron	N/A	NP_004000.1	P11532
	DMD	NM_000109.4		c.7848+6513G>A		intron	N/A	NP_000100.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMD	ENST00000357033.9	TSL:1 MANE Select	c.7872+6513G>A		intron	N/A	ENSP00000354923.3	P11532-1
	DMD	ENST00000378677.6	TSL:5	c.7860+6513G>A		intron	N/A	ENSP00000367948.2	P11532-11
	DMD	ENST00000619831.5	TSL:5	c.3840+6513G>A		intron	N/A	ENSP00000479270.2	A0A087WV90

Frequencies

GnomAD3 genomes AF: 0.406 AC: 44926 AN: 110764 Hom.: 7476 Cov.: 23

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

African (AFR) AF: 0.612 AC: 18598 AN: 30381

American (AMR) AF: 0.415 AC: 4316 AN: 10411

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 790 AN: 2638

East Asian (EAS) AF: 0.446 AC: 1558 AN: 3495

South Asian (SAS) AF: 0.255 AC: 676 AN: 2654

European-Finnish (FIN) AF: 0.237 AC: 1405 AN: 5938

Middle Eastern (MID) AF: 0.400 AC: 86 AN: 215

European-Non Finnish (NFE) AF: 0.316 AC: 16745 AN: 52908

Other (OTH) AF: 0.433 AC: 657 AN: 1518

Alfa AF: 0.362 Hom.: 12563

Bravo AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.22
DANN	Benign	0.53
PhyloP100		-1.0
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: rs5971587; hg19: chrX-31690979;