14-23412977-T-G

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.5791-106A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,181,558 control chromosomes in the GnomAD database, including 81,528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 15798 hom., cov: 32)

Exomes 𝑓: 0.34 ( 65730 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.27

Publications

4 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
MYH7-related skeletal myopathy
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
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=-0.87).

BP6

Variant 14-23412977-T-G is Benign according to our data. Variant chr14-23412977-T-G is described in ClinVar as Benign. ClinVar VariationId is 671943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7	NM_000257.4 link	c.5791-106A>C		intron_variant	Intron 39 of 39	ENST00000355349.4	NP_000248.2	P12883
MYH7	NM_001407004.1 link	c.5791-106A>C		intron_variant	Intron 38 of 38		NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH7	ENST00000355349.4 link	c.5791-106A>C	intron_variant	Intron 39 of 39	1	NM_000257.4	ENSP00000347507.3	P12883
MYH7	ENST00000713768.1 link	c.*32-106A>C	intron_variant	Intron 40 of 40			ENSP00000519070.1
MYH7	ENST00000713769.1 link	c.5791-106A>C	intron_variant	Intron 38 of 38			ENSP00000519071.1

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64264

AN:

151922

Hom.:

15764

Cov.:

show subpopulations

Gnomad AFR

AF:

0.677

Gnomad AMI

AF:

0.432

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.0684

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.417

GnomAD4 exome

AF:

0.344

AC:

354105

AN:

1029520

Hom.:

65730

AF XY:

0.340

AC XY:

179768

AN XY:

528762

show subpopulations

African (AFR)

AF:

0.680

AC:

16926

AN:

24882

American (AMR)

AF:

0.206

AC:

8187

AN:

39830

Ashkenazi Jewish (ASJ)

AF:

0.403

AC:

9395

AN:

23304

East Asian (EAS)

AF:

0.0456

AC:

1677

AN:

36802

South Asian (SAS)

AF:

0.239

AC:

18129

AN:

75820

European-Finnish (FIN)

AF:

0.275

AC:

11638

AN:

42388

Middle Eastern (MID)

AF:

0.314

AC:

1552

AN:

4938

European-Non Finnish (NFE)

AF:

0.368

AC:

270283

AN:

735128

Other (OTH)

AF:

0.351

AC:

16318

AN:

46428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

11588

23177

34765

46354

57942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6972

13944

20916

27888

34860

<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:

0.423

AC:

64333

AN:

152038

Hom.:

15798

Cov.:

AF XY:

0.410

AC XY:

30439

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.677

AC:

28091

AN:

41480

American (AMR)

AF:

0.292

AC:

4455

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

1355

AN:

3466

East Asian (EAS)

AF:

0.0686

AC:

355

AN:

5176

South Asian (SAS)

AF:

0.229

AC:

1102

AN:

4816

European-Finnish (FIN)

AF:

0.263

AC:

2779

AN:

10568

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.366

AC:

24839

AN:

67938

Other (OTH)

AF:

0.412

AC:

870

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1729

3458

5188

6917

8646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.407

Hom.:

1725

Bravo

AF:

0.434

Asia WGS

AF:

0.184

AC:

642

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.35

(source)

DANN

Benign

0.62

PhyloP100

-1.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over