rs3729810

Variant names:

Variant summary

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

The NM_000257.4(MYH7):c.999+44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 1,508,828 control chromosomes in the GnomAD database, including 11,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 4003 hom., cov: 32)

Exomes 𝑓: 0.087 ( 7446 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.265

Publications

6 publications found

Variant links:

Genes affected

MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]

MYH7 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dilated cardiomyopathy 1S
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
MYH7-related skeletal myopathy
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
myopathy, myosin storage, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
myopathy, myosin storage, autosomal dominant
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
congenital myopathy 7A, myosin storage, autosomal dominant
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Ebstein anomaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hyaline body myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
left ventricular noncompaction
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

MYH7 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 (BayesDel_noAF=-0.82).

BP6

Variant 14-23430516-A-G is Benign according to our data. Variant chr14-23430516-A-G is described in ClinVar as Benign. ClinVar VariationId is 255636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000257.4. 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
	MYH7	NM_000257.4	MANE Select	c.999+44T>C		intron	N/A	NP_000248.2	P12883
	MYH7	NM_001407004.1		c.999+44T>C		intron	N/A	NP_001393933.1	P12883

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYH7	ENST00000355349.4	TSL:1 MANE Select	c.999+44T>C	intron	N/A	ENSP00000347507.3	P12883
MYH7	ENST00000858540.1		c.999+44T>C	intron	N/A	ENSP00000528599.1
MYH7	ENST00000965955.1		c.999+44T>C	intron	N/A	ENSP00000636014.1

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26175

AN:

151774

Hom.:

3989

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0948

Gnomad ASJ

AF:

0.0972

Gnomad EAS

AF:

0.0161

Gnomad SAS

AF:

0.0798

Gnomad FIN

AF:

0.0566

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0834

Gnomad OTH

AF:

0.156

GnomAD2 exomes

AF:

0.0951

AC:

22185

AN:

233304

AF XY:

0.0908

show subpopulations

Gnomad AFR exome

AF:

0.423

Gnomad AMR exome

AF:

0.0618

Gnomad ASJ exome

AF:

0.0986

Gnomad EAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.0549

Gnomad NFE exome

AF:

0.0840

Gnomad OTH exome

AF:

0.0941

GnomAD4 exome

AF:

0.0875

AC:

118718

AN:

1356936

Hom.:

7446

Cov.:

AF XY:

0.0866

AC XY:

58831

AN XY:

679258

show subpopulations

African (AFR)

AF:

0.430

AC:

13458

AN:

31306

American (AMR)

AF:

0.0664

AC:

2814

AN:

42394

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

2551

AN:

25300

East Asian (EAS)

AF:

0.0120

AC:

467

AN:

39064

South Asian (SAS)

AF:

0.0796

AC:

6580

AN:

82664

European-Finnish (FIN)

AF:

0.0563

AC:

2975

AN:

52814

Middle Eastern (MID)

AF:

0.134

AC:

744

AN:

5570

European-Non Finnish (NFE)

AF:

0.0814

AC:

83089

AN:

1020824

Other (OTH)

AF:

0.106

AC:

6040

AN:

57000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5747

11494

17242

22989

28736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3068

6136

9204

12272

15340

<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:

0.173

AC:

26233

AN:

151892

Hom.:

4003

Cov.:

AF XY:

0.166

AC XY:

12290

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.418

AC:

17293

AN:

41364

American (AMR)

AF:

0.0946

AC:

1443

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.0972

AC:

337

AN:

3466

East Asian (EAS)

AF:

0.0159

AC:

AN:

5158

South Asian (SAS)

AF:

0.0799

AC:

384

AN:

4808

European-Finnish (FIN)

AF:

0.0566

AC:

598

AN:

10564

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0834

AC:

5667

AN:

67960

Other (OTH)

AF:

0.163

AC:

344

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

927

1853

2780

3706

4633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<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:

0.131

Hom.:

488

Bravo

AF:

0.186

Asia WGS

AF:

0.0890

AC:

307

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.1

(source)

DANN

Benign

0.74

PhyloP100

-0.27

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

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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