rs716354

Variant names:

• chrX-31615975-G-A
• rs716354
• NM_004006.3:c.8217+11698C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-31615975-G-A
• chrX-31615975-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004006.3(DMD):​c.8217+11698C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 110,892 control chromosomes in the GnomAD database, including 5,973 homozygotes. There are 11,507 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 0.36 (5973 hom., 11507 hem., cov: 23)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168
• Publications: 0 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3	c.8217+11698C>T		intron_variant	Intron 55 of 78	ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.8217+11698C>T		intron_variant	Intron 55 of 78	1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes AF: 0.364 AC: 40346 AN: 110836 Hom.: 5968 Cov.: 23

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.364 AC: 40400 AN: 110892 Hom.: 5973 Cov.: 23 AF XY: 0.347 AC XY: 11507 AN XY: 33164

African (AFR) AF: 0.548 AC: 16659 AN: 30420

American (AMR) AF: 0.389 AC: 4046 AN: 10404

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 706 AN: 2643

East Asian (EAS) AF: 0.340 AC: 1186 AN: 3489

South Asian (SAS) AF: 0.242 AC: 635 AN: 2625

European-Finnish (FIN) AF: 0.224 AC: 1333 AN: 5963

Middle Eastern (MID) AF: 0.381 AC: 82 AN: 215

European-Non Finnish (NFE) AF: 0.284 AC: 15010 AN: 52945

Other (OTH) AF: 0.389 AC: 587 AN: 1509

Alfa AF: 0.324 Hom.: 37806

Bravo AF: 0.391

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.57
PhyloP100		0.17
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: rs716354; hg19: chrX-31634092;