16-15757820-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_002474.3(MYH11):c.1575+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000905 in 1,614,062 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002474.3 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_001040113.2 | c.1596+7G>A | splice_region_variant, intron_variant | ENST00000452625.7 | |||
MYH11 | NM_002474.3 | c.1575+7G>A | splice_region_variant, intron_variant | ENST00000300036.6 | |||
MYH11 | NM_001040114.2 | c.1596+7G>A | splice_region_variant, intron_variant | ||||
MYH11 | NM_022844.3 | c.1575+7G>A | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.1575+7G>A | splice_region_variant, intron_variant | 1 | NM_002474.3 | P3 | |||
MYH11 | ENST00000452625.7 | c.1596+7G>A | splice_region_variant, intron_variant | 1 | NM_001040113.2 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152054Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000160 AC: 40AN: 250772Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135622
GnomAD4 exome AF: 0.0000958 AC: 140AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.000106 AC XY: 77AN XY: 727248
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152172Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74428
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | MYH11: PM2, BP4 - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 2017 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 02, 2017 | Variant summary: The MYH11 c.1596+7G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 3/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 39/245582 control chromosomes at a frequency of 0.0001588, which is approximately 127 times the estimated maximal expected allele frequency of a pathogenic MYH11 variant (0.0000013), suggesting this variant is likely a benign polymorphism. In addition, a clinical diagnostic laboratory/reputable database classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. - |
Aortic aneurysm, familial thoracic 4 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 15, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Dec 09, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at