chr14-23412741-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000257.4(MYH7):c.*113G>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 1,298,592 control chromosomes in the GnomAD database, including 3,967 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 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
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH7 | NM_000257.4 | c.*113G>A | splice_region_variant | Exon 40 of 40 | ENST00000355349.4 | NP_000248.2 | ||
MYH7 | NM_000257.4 | c.*113G>A | 3_prime_UTR_variant | Exon 40 of 40 | ENST00000355349.4 | NP_000248.2 | ||
MYH7 | NM_001407004.1 | c.*113G>A | splice_region_variant | Exon 39 of 39 | NP_001393933.1 | |||
MYH7 | NM_001407004.1 | c.*113G>A | 3_prime_UTR_variant | Exon 39 of 39 | NP_001393933.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0659 AC: 10028AN: 152130Hom.: 400 Cov.: 32
GnomAD4 exome AF: 0.0766 AC: 87808AN: 1146342Hom.: 3568 Cov.: 15 AF XY: 0.0783 AC XY: 45604AN XY: 582680
GnomAD4 genome AF: 0.0658 AC: 10020AN: 152250Hom.: 399 Cov.: 32 AF XY: 0.0660 AC XY: 4910AN XY: 74432
ClinVar
Submissions by phenotype
not specified Benign:2
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Dilated Cardiomyopathy, Dominant Benign:2
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not provided Benign:2
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Scapuloperoneal myopathy Benign:1
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MYH7-related skeletal myopathy Benign:1
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Myosin storage myopathy Benign:1
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Atrial septal defect Benign:1
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Left ventricular noncompaction cardiomyopathy Benign:1
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Hypertrophic cardiomyopathy Benign:1
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Hypertrophic cardiomyopathy 1 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at