rs28715870

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004006.3(DMD):c.4162T>G(p.Phe1388Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,208,952 control chromosomes in the GnomAD database, including 158 homozygotes. There are 1,659 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 89 hom., 777 hem., cov: 22)

Exomes 𝑓: 0.0029 ( 69 hom. 882 hem. )

Consequence

DMD
NM_004006.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: 1.47

Publications

3 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022250712).

BP6

Variant X-32411823-A-C is Benign according to our data. Variant chrX-32411823-A-C is described in ClinVar as Benign. ClinVar VariationId is 94615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0837 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DMD	NM_004006.3	MANE Select	c.4162T>G	p.Phe1388Val	missense	Exon 30 of 79	NP_003997.2	P11532-1
DMD	NM_004009.3		c.4150T>G	p.Phe1384Val	missense	Exon 30 of 79	NP_004000.1	P11532
DMD	NM_000109.4		c.4138T>G	p.Phe1380Val	missense	Exon 30 of 79	NP_000100.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DMD	ENST00000357033.9	TSL:1 MANE Select	c.4162T>G	p.Phe1388Val	missense	Exon 30 of 79	ENSP00000354923.3	P11532-1
DMD	ENST00000378677.6	TSL:5	c.4150T>G	p.Phe1384Val	missense	Exon 30 of 79	ENSP00000367948.2	P11532-11
DMD	ENST00000619831.5	TSL:5	c.130T>G	p.Phe44Val	missense	Exon 2 of 51	ENSP00000479270.2	A0A087WV90

Frequencies

GnomAD3 genomes

AF:

0.0256

AC:

2846

AN:

111321

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0860

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0142

Gnomad ASJ

AF:

0.00189

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00339

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000452

Gnomad OTH

AF:

0.0200

GnomAD2 exomes

AF:

0.00767

AC:

1403

AN:

182914

AF XY:

0.00539

show subpopulations

Gnomad AFR exome

AF:

0.0892

Gnomad AMR exome

AF:

0.00577

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000319

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00287

AC:

3153

AN:

1097580

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

882

AN XY:

363016

show subpopulations

African (AFR)

AF:

0.0855

AC:

2256

AN:

26380

American (AMR)

AF:

0.00662

AC:

233

AN:

35200

Ashkenazi Jewish (ASJ)

AF:

0.00150

AC:

AN:

19378

East Asian (EAS)

AF:

0.00

AC:

AN:

30167

South Asian (SAS)

AF:

0.00122

AC:

AN:

54130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40516

Middle Eastern (MID)

AF:

0.00508

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.000270

AC:

227

AN:

841607

Other (OTH)

AF:

0.00697

AC:

321

AN:

46067

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

133

266

398

531

664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.0257

AC:

2864

AN:

111372

Hom.:

Cov.:

AF XY:

0.0231

AC XY:

777

AN XY:

33580

show subpopulations

African (AFR)

AF:

0.0865

AC:

2648

AN:

30629

American (AMR)

AF:

0.0142

AC:

148

AN:

10443

Ashkenazi Jewish (ASJ)

AF:

0.00189

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3510

South Asian (SAS)

AF:

0.00302

AC:

AN:

2650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5949

Middle Eastern (MID)

AF:

0.00459

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000452

AC:

AN:

53129

Other (OTH)

AF:

0.0198

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

192

287

383

479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0104

Hom.:

719

Bravo

AF:

0.0292

ESP6500AA

AF:

0.0900

AC:

345

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.00872

AC:

1059

EpiCase

AF:

0.000327

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (9)

not provided (3)

Cardiovascular phenotype (1)

Dilated cardiomyopathy 3B (1)

Duchenne muscular dystrophy (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.92

BayesDel_noAF

Benign

-1.0

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.22

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.0

PhyloP100

1.5

PrimateAI

Benign

0.32

PROVEAN

Benign

0.020

REVEL

Benign

0.024

Sift

Benign

0.26

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.055

MVP

0.15

MPC

0.016

ClinPred

0.0017

GERP RS

3.1

PromoterAI

0.020

Neutral

(source)

gMVP

0.081

Mutation Taster

=99/1

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

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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