rs376604168
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1
The NM_000257.4(MYH7):c.4953+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,614,124 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00017 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
MYH7
NM_000257.4 intron
NM_000257.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.185
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 14-23415987-C-T is Benign according to our data. Variant chr14-23415987-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23415987-C-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000119 (174/1461806) while in subpopulation MID AF= 0.00471 (27/5734). AF 95% confidence interval is 0.00332. There are 0 homozygotes in gnomad4_exome. There are 95 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH7 | NM_000257.4 | c.4953+17G>A | intron_variant | ENST00000355349.4 | |||
MHRT | NR_126491.1 | n.262-14C>T | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | ||||
MYH7 | NM_001407004.1 | c.4953+17G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH7 | ENST00000355349.4 | c.4953+17G>A | intron_variant | 1 | NM_000257.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152200Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000179 AC: 45AN: 250996Hom.: 0 AF XY: 0.000169 AC XY: 23AN XY: 135714
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GnomAD4 exome AF: 0.000119 AC: 174AN: 1461806Hom.: 0 Cov.: 34 AF XY: 0.000131 AC XY: 95AN XY: 727210
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GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152318Hom.: 1 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74486
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 26, 2023 | - - |
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at