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rs2284651

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000257.4(MYH7):c.5791-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,562,884 control chromosomes in the GnomAD database, including 115,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.44 ( 16634 hom., cov: 32)
Exomes 𝑓: 0.36 ( 98491 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.89
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
Variant 14-23412935-T-C is Benign according to our data. Variant chr14-23412935-T-C is described in ClinVar as [Benign]. Clinvar id is 1263654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23412935-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYH7NM_000257.4 linkuse as main transcriptc.5791-64A>G intron_variant ENST00000355349.4
MYH7NM_001407004.1 linkuse as main transcriptc.5791-64A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYH7ENST00000355349.4 linkuse as main transcriptc.5791-64A>G intron_variant 1 NM_000257.4 P1

Frequencies

GnomAD3 genomes
AF:
0.438
AC:
66576
AN:
151902
Hom.:
16591
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.687
Gnomad AMI
AF:
0.434
Gnomad AMR
AF:
0.316
Gnomad ASJ
AF:
0.426
Gnomad EAS
AF:
0.154
Gnomad SAS
AF:
0.269
Gnomad FIN
AF:
0.269
Gnomad MID
AF:
0.405
Gnomad NFE
AF:
0.375
Gnomad OTH
AF:
0.449
GnomAD4 exome
AF:
0.364
AC:
514117
AN:
1410864
Hom.:
98491
AF XY:
0.361
AC XY:
254578
AN XY:
704664
show subpopulations
Gnomad4 AFR exome
AF:
0.696
Gnomad4 AMR exome
AF:
0.237
Gnomad4 ASJ exome
AF:
0.438
Gnomad4 EAS exome
AF:
0.136
Gnomad4 SAS exome
AF:
0.271
Gnomad4 FIN exome
AF:
0.280
Gnomad4 NFE exome
AF:
0.377
Gnomad4 OTH exome
AF:
0.372
GnomAD4 genome
AF:
0.439
AC:
66666
AN:
152020
Hom.:
16634
Cov.:
32
AF XY:
0.426
AC XY:
31666
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.687
Gnomad4 AMR
AF:
0.316
Gnomad4 ASJ
AF:
0.426
Gnomad4 EAS
AF:
0.154
Gnomad4 SAS
AF:
0.268
Gnomad4 FIN
AF:
0.269
Gnomad4 NFE
AF:
0.375
Gnomad4 OTH
AF:
0.452
Alfa
AF:
0.347
Hom.:
2094
Bravo
AF:
0.452
Asia WGS
AF:
0.272
AC:
947
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
Cadd
Benign
0.075
Dann
Benign
0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2284651; hg19: chr14-23882144; COSMIC: COSV62519821; COSMIC: COSV62519821; API