rs754494548
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_002474.3(MYH11):c.1968G>A(p.Leu656=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,094 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 1 hom. )
Consequence
MYH11
NM_002474.3 synonymous
NM_002474.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.677
Genes affected
MYH11 (HGNC:7569): (myosin heavy chain 11) The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. A chromosomal rearrangement involving this gene is associated with acute myeloid leukemia of the M4Eo subtype. Mutations in this gene are associated with visceral myopathy, megacystis-microcolon-intestinal hypoperistalsis syndrome 2, and familial thoracic aortic aneurysm 4. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
Variant 16-15750228-C-T is Benign according to our data. Variant chr16-15750228-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 465709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.677 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000253 (37/1461882) while in subpopulation AMR AF= 0.000827 (37/44724). AF 95% confidence interval is 0.000617. There are 1 homozygotes in gnomad4_exome. There are 17 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 |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.1968G>A | p.Leu656= | synonymous_variant | 16/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.1989G>A | p.Leu663= | synonymous_variant | 17/43 | ENST00000452625.7 | |
MYH11 | NM_001040114.2 | c.1989G>A | p.Leu663= | synonymous_variant | 17/42 | ||
MYH11 | NM_022844.3 | c.1968G>A | p.Leu656= | synonymous_variant | 16/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.1968G>A | p.Leu656= | synonymous_variant | 16/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.1989G>A | p.Leu663= | synonymous_variant | 17/43 | 1 | NM_001040113.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000127 AC: 32AN: 251294Hom.: 1 AF XY: 0.000118 AC XY: 16AN XY: 135856
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461882Hom.: 1 Cov.: 34 AF XY: 0.0000234 AC XY: 17AN XY: 727240
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74366
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Feb 16, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 18, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 02, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Aortic aneurysm, familial thoracic 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 25, 2023 | - - |
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