chr19-38565185-G-GCACGGCGGC
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3BP6BS1BS2
The NM_000540.3(RYR1):c.12861_12869dupCACGGCGGC(p.Ala4290_Ala4291insThrAlaAla) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,117,934 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000540.3 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00745 AC: 1099AN: 147504Hom.: 14 Cov.: 32
GnomAD4 exome AF: 0.000654 AC: 635AN: 970324Hom.: 10 Cov.: 29 AF XY: 0.000644 AC XY: 294AN XY: 456650
GnomAD4 genome AF: 0.00749 AC: 1106AN: 147610Hom.: 15 Cov.: 32 AF XY: 0.00726 AC XY: 522AN XY: 71946
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
RYR1: BS1, BS2 -
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This variant is associated with the following publications: (PMID: 30611313, 28326467, 27663056, 26972305, 23476141, 23628358, 23394784, 19807743, 19191329) -
not specified Uncertain:1Benign:1
The p.Ala4290_Ala4291insThrAlaAla variant in RYR1 is classified as benign because it has been identified in 2.53% (205/8116) of African/African-American chromosomes, including 3 homozygotes, by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA -
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RYR1-related disorder Benign:2
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
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Inborn genetic diseases Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at