dbSNP rs149479376: DMD:c.8218-798G>A (chrX-31508251-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_004014.3(DMD):c.-14G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000612 in 1,204,902 control chromosomes in the GnomAD database, including 8 homozygotes. There are 200 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 4 hom., 73 hem., cov: 22)

Exomes 𝑓: 0.00039 ( 4 hom. 127 hem. )

Consequence

DMD
NM_004014.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.91

Publications

1 publications found

Variant links:

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

DMD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant X-31508251-C-T is Benign according to our data. Variant chrX-31508251-C-T is described in ClinVar as Benign. ClinVar VariationId is 226568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00281 (313/111301) while in subpopulation AFR AF = 0.00966 (296/30630). AF 95% confidence interval is 0.00876. There are 4 homozygotes in GnomAd4. There are 73 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High AC in GnomAd4 at 313 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004014.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DMD	NM_004006.3	MANE Select	c.8218-798G>A	intron	N/A	NP_003997.2	P11532-1
DMD	NM_004014.3		c.-14G>A	5_prime_UTR	Exon 1 of 25	NP_004005.2	P11532-17
DMD	NM_004009.3		c.8206-798G>A	intron	N/A	NP_004000.1	P11532

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DMD	ENST00000357033.9	TSL:1 MANE Select	c.8218-798G>A		intron	N/A	ENSP00000354923.3	P11532-1
DMD	ENST00000343523.7	TSL:5	c.29G>A	p.Arg10Gln	missense	Exon 1 of 25	ENSP00000340057.4	A0A5H1ZRP7
DMD	ENST00000378677.6	TSL:5	c.8206-798G>A		intron	N/A	ENSP00000367948.2	P11532-11

Frequencies

GnomAD3 genomes

AF:

0.00279

AC:

310

AN:

111248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00959

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00200

GnomAD2 exomes

AF:

0.000825

AC:

146

AN:

176863

AF XY:

0.000523

show subpopulations

Gnomad AFR exome

AF:

0.0106

Gnomad AMR exome

AF:

0.000444

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000508

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.000388

AC:

424

AN:

1093601

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

127

AN XY:

359357

show subpopulations

African (AFR)

AF:

0.0108

AC:

285

AN:

26318

American (AMR)

AF:

0.000543

AC:

AN:

35010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19268

East Asian (EAS)

AF:

0.00

AC:

AN:

30042

South Asian (SAS)

AF:

0.0000560

AC:

AN:

53602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40258

Middle Eastern (MID)

AF:

0.000486

AC:

AN:

4118

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

839139

Other (OTH)

AF:

0.000894

AC:

AN:

45846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00281

AC:

313

AN:

111301

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

AN XY:

33519

show subpopulations

African (AFR)

AF:

0.00966

AC:

296

AN:

30630

American (AMR)

AF:

0.00125

AC:

AN:

10434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2641

East Asian (EAS)

AF:

0.00

AC:

AN:

3532

South Asian (SAS)

AF:

0.00

AC:

AN:

2616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5953

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53072

Other (OTH)

AF:

0.00197

AC:

AN:

1522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000401

Hom.:

Bravo

AF:

0.00332

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

2.9

PromoterAI

-0.0091

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over