NM_000257.4:c.639+9G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000257.4(MYH7):​c.639+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0600

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 14-23431752-C-T is Benign according to our data. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-T is described in CliVar as Likely_benign. Clinvar id is 525114.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYH7NM_000257.4 linkc.639+9G>A intron_variant Intron 7 of 39 ENST00000355349.4 NP_000248.2 P12883
MYH7NM_001407004.1 linkc.639+9G>A intron_variant Intron 6 of 38 NP_001393933.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYH7ENST00000355349.4 linkc.639+9G>A intron_variant Intron 7 of 39 1 NM_000257.4 ENSP00000347507.3 P12883
MYH7ENST00000713768.1 linkc.639+9G>A intron_variant Intron 7 of 40 ENSP00000519070.1
MYH7ENST00000713769.1 linkc.639+9G>A intron_variant Intron 6 of 38 ENSP00000519071.1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152258
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461832
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727230
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000348
AC:
3
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111952
Other (OTH)
AF:
0.00
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152258
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74376
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
41478
American (AMR)
AF:
0.00
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5196
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10630
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68040
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hypertrophic cardiomyopathy Benign:1
Apr 03, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
2.8
DANN
Benign
0.70
PhyloP100
-0.060

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

Other links and lift over

dbSNP: rs373301620; hg19: chr14-23900961; API