Evidence Repository
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.-108T>C

CA023868

132987 (ClinVar)

Gene: RYR1
Condition: RYR1-related myopathy
Inheritance Mode: Undetermined mode of inheritance
Link to MONDO
UUID: d426b788-b21b-4329-8ddb-1783bea6421c
Approved on: 2024-08-07
Published on: 2024-10-02

HGVS expressions

NM_000540.3:c.-108T>C
NM_000540.3(RYR1):c.-108T>C
NC_000019.10:g.38433722T>C
CM000681.2:g.38433722T>C
NC_000019.9:g.38924362T>C
CM000681.1:g.38924362T>C
NC_000019.8:g.43616202T>C
NG_008866.1:g.5023T>C
ENST00000359596.8:c.-108T>C
ENST00000355481.8:c.-108T>C
NM_000540.2:c.-108T>C
NM_001042723.1:c.-108T>C
NM_001042723.2:c.-108T>C
More

Benign

Met criteria codes 3
BA1 BP7 BP4
Not Met criteria codes 9
PS1 PS3 PM2 PM4 PM5 PVS1 BS3 BS1 BP3

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 NM_000540.3:c.-108T>C variant is located in exon 1 (5’ UTR) of the RYR1 gene. The filtering allele frequency (the lower threshold of the 95% CI of 8126/59394, 618 homozygotes) of the c.-108T>C variant in RYR1 is 0.1297 for African/African American 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). This variant is not predicted to impact splicing by SpliceAI. In addition, it occurs at a nucleotide that is poorly conserved as shown by the UCSC Genome Browser (BP4, BP7). In summary, the variant meets the criteria to be classified as benign for RYR1-related myopathy. ACMG/AMP criteria met, as specified by the ClinGen 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 8126/59394) of the c.-108T>C variant in RYR1 is 0.1297 for African/African American 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 predicts no impact on splicing
BP4
Poorly conserved in UCSC genome browser
Not Met criteria codes
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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