rs369286647
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_000257.4(MYH7):c.796+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 0.0000421 in 1,613,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000257.4 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH7 | NM_000257.4 | c.796+7G>A | splice_region_variant, intron_variant | ENST00000355349.4 | |||
MYH7 | NM_001407004.1 | c.796+7G>A | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH7 | ENST00000355349.4 | c.796+7G>A | splice_region_variant, intron_variant | 1 | NM_000257.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000994 AC: 25AN: 251426Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135886
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1461522Hom.: 0 Cov.: 33 AF XY: 0.0000316 AC XY: 23AN XY: 727094
GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74478
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 09, 2022 | Variant summary: MYH7 c.796+7G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00018 in 152182 control chromosomes, predominantly at a frequency of 0.0012 within the African or African-American subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in MYH7 causing Cardiomyopathy (0.00018 vs 0.0013), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.796+7G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 27, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 22, 2014 | 796+7G>A in intron 9 of MYH7: This variant is not expected to have clinical sign ificance because it is not located within the splice consensus sequence. It has been identified in 2/4406 African American chromosomes by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs369286647). - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Nov 11, 2021 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at