The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000540.3(RYR1):c.8400+28A>G

CA024918

133224 (ClinVar)

Gene: RYR1
Condition: RYR1-related myopathy
Inheritance Mode: Undetermined mode of inheritance
UUID: 4d311f52-bcc3-4fa7-b690-a1199c7ef05f
Approved on: 2024-08-07
Published on: 2024-10-02

HGVS expressions

NM_000540.3:c.8400+28A>G
NM_000540.3(RYR1):c.8400+28A>G
NC_000019.10:g.38505426A>G
CM000681.2:g.38505426A>G
NC_000019.9:g.38996066A>G
CM000681.1:g.38996066A>G
NC_000019.8:g.43687906A>G
NG_008866.1:g.76727A>G
ENST00000599547.6:c.8400+28A>G
ENST00000359596.8:c.8400+28A>G
ENST00000355481.8:c.8400+28A>G
ENST00000359596.7:c.8400+28A>G
ENST00000360985.7:c.8397+28A>G
ENST00000594335.5:c.1852+28A>G
NM_000540.2:c.8400+28A>G
NM_001042723.1:c.8400+28A>G
NM_001042723.2:c.8400+28A>G
More

Benign

Met criteria codes 3
BA1 BP7 BP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Congenital Myopathies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RYR1 Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Congenital Myopathies VCEP
The variant NM_000540.3:c.8400+28A>G in RYR1 is an intronic variant located in intron 53. The filtering allele frequency (the lower threshold of the 95% CI of 37922/85572, 8751 homozygotes) of the c.8400+28A>G variant in RYR1 is 0.4383 for South Asian chromosomes by gnomAD v4.1, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.00697) for BA1, and therefore meets this criterion (BA1). The c.8400+28A>G variant is an intronic variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by UCSC Genome Browser (BP4, BP7). In summary, the variant meets criteria to be classified as benign. ACMG/AMP criteria met, as specified by the congenital myopathies VCEP: BA1, BP4, BP7 (ClinGen Congenital Myopathies VCEP specifications version 1; 8/7/2024).
Met criteria codes
BA1
The filtering allele frequency (the lower threshold of the 95% CI of 37922/85572, 8751 homozygotes) of the c.8400+28A>G variant in RYR1 is 0.4383 for South Asian chromosomes by gnomAD v4.1, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.00697) for BA1, and therefore meets this criterion (BA1).
BP7
SpliceAI predicted no impact on splicing, meeting BP4/BP7 criteria.
BP4
SpliceAI predicted no impact on splicing, meeting BP4/BP7 criteria.
Curation History
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