chr14-23417200-G-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.4472C>G (p.Ser1491Cys) variant in the MYH7 gene is 0.98% (698/66740) of European chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; PMID:29300372). LINK:https://erepo.genome.network/evrepo/ui/classification/CA015008/MONDO:0004994/002
Frequency
Consequence
NM_000257.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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MYH7 | NM_000257.4 | c.4472C>G | p.Ser1491Cys | missense_variant | Exon 32 of 40 | ENST00000355349.4 | NP_000248.2 | |
MYH7 | NM_001407004.1 | c.4472C>G | p.Ser1491Cys | missense_variant | Exon 31 of 39 | NP_001393933.1 | ||
MHRT | NR_126491.1 | n.652-12G>C | intron_variant | Intron 4 of 5 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00854 AC: 1299AN: 152148Hom.: 13 Cov.: 33
GnomAD3 exomes AF: 0.00818 AC: 2058AN: 251494Hom.: 16 AF XY: 0.00836 AC XY: 1136AN XY: 135922
GnomAD4 exome AF: 0.0119 AC: 17342AN: 1461892Hom.: 143 Cov.: 34 AF XY: 0.0117 AC XY: 8506AN XY: 727248
GnomAD4 genome AF: 0.00854 AC: 1300AN: 152266Hom.: 13 Cov.: 33 AF XY: 0.00786 AC XY: 585AN XY: 74468
ClinVar
Submissions by phenotype
not specified Benign:10
p.Ser1491Cys in exon 31 of MYH7: This variant is not expected to have clinical s ignificance because it has been identified in 1.1% (698/66740) of European chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs3729823). -
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. -
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not provided Benign:5
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MYH7: BS1, BS2 -
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Hypertrophic cardiomyopathy Benign:3
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Cardiomyopathy Benign:2
The filtering allele frequency of the c.4472C>G (p.Ser1491Cys) variant in the MYH7 gene is 0.98% (698/66740) of European chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; PMID:29300372). -
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Hypertrophic cardiomyopathy 1 Benign:2
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
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Dilated cardiomyopathy 1S Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Hypertrophic cardiomyopathy;C0007196:Restrictive cardiomyopathy;C0878544:Cardiomyopathy Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at