rs200223639
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_002474.3(MYH11):c.4579-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,613,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_002474.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_001040113.2 | c.4600-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000452625.7 | |||
MYH11 | NM_002474.3 | c.4579-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000300036.6 | |||
NDE1 | NM_017668.3 | c.948-3134G>A | intron_variant | ENST00000396354.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.4579-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002474.3 | P3 | |||
NDE1 | ENST00000396354.6 | c.948-3134G>A | intron_variant | 1 | NM_017668.3 | P1 | |||
MYH11 | ENST00000452625.7 | c.4600-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001040113.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152002Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000997 AC: 25AN: 250814Hom.: 0 AF XY: 0.0000885 AC XY: 12AN XY: 135664
GnomAD4 exome AF: 0.0000520 AC: 76AN: 1461354Hom.: 0 Cov.: 32 AF XY: 0.0000426 AC XY: 31AN XY: 727018
GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152120Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6AN XY: 74376
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:2
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jan 31, 2019 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 21, 2016 | 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. - |
Aortic aneurysm, familial thoracic 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2023 | - - |
See cases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University Hospital Muenster | Jun 13, 2022 | ACMG categories: BP4,BP6 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at