rs439735
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002471.4(MYH6):c.1582-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,608,864 control chromosomes in the GnomAD database, including 49,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.22 ( 4079 hom., cov: 31)
Exomes 𝑓: 0.24 ( 45035 hom. )
Consequence
MYH6
NM_002471.4 intron
NM_002471.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0950
Genes affected
MYH6 (HGNC:7576): (myosin heavy chain 6) Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 14-23399076-G-A is Benign according to our data. Variant chr14-23399076-G-A is described in ClinVar as [Benign]. Clinvar id is 258706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23399076-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.1582-39C>T | intron_variant | ENST00000405093.9 | NP_002462.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.1582-39C>T | intron_variant | 5 | NM_002471.4 | ENSP00000386041 | P1 |
Frequencies
GnomAD3 genomes AF: 0.225 AC: 34122AN: 151824Hom.: 4081 Cov.: 31
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GnomAD3 exomes AF: 0.210 AC: 52154AN: 248560Hom.: 6004 AF XY: 0.214 AC XY: 28824AN XY: 134610
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GnomAD4 exome AF: 0.244 AC: 355222AN: 1456922Hom.: 45035 Cov.: 32 AF XY: 0.243 AC XY: 175981AN XY: 725090
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GnomAD4 genome AF: 0.225 AC: 34134AN: 151942Hom.: 4079 Cov.: 31 AF XY: 0.222 AC XY: 16516AN XY: 74270
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
BranchPoint Hunter
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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