chr19-38504715-ACCT-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000540.3(RYR1):​c.8068-29_8068-27del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,611,506 control chromosomes in the GnomAD database, including 68,568 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9153 hom., cov: 0)
Exomes 𝑓: 0.28 ( 59415 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.613
Variant links:
Genes affected
RYR1 (HGNC:10483): (ryanodine receptor 1) This gene encodes a ryanodine receptor found in skeletal muscle. The encoded protein functions as a calcium release channel in the sarcoplasmic reticulum but also serves to connect the sarcoplasmic reticulum and transverse tubule. Mutations in this gene are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 19-38504715-ACCT-A is Benign according to our data. Variant chr19-38504715-ACCT-A is described in ClinVar as [Benign]. Clinvar id is 256570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RYR1NM_000540.3 linkuse as main transcriptc.8068-29_8068-27del intron_variant ENST00000359596.8 NP_000531.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RYR1ENST00000359596.8 linkuse as main transcriptc.8068-29_8068-27del intron_variant 5 NM_000540.3 ENSP00000352608 A2P21817-1
RYR1ENST00000355481.8 linkuse as main transcriptc.8068-29_8068-27del intron_variant 1 ENSP00000347667 P4P21817-2
RYR1ENST00000594335.5 linkuse as main transcriptc.1520-29_1520-27del intron_variant, NMD_transcript_variant 1 ENSP00000470927
RYR1ENST00000599547.6 linkuse as main transcriptc.8068-29_8068-27del intron_variant, NMD_transcript_variant 2 ENSP00000471601

Frequencies

GnomAD3 genomes
AF:
0.334
AC:
50542
AN:
151246
Hom.:
9111
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.459
Gnomad AMI
AF:
0.260
Gnomad AMR
AF:
0.358
Gnomad ASJ
AF:
0.269
Gnomad EAS
AF:
0.360
Gnomad SAS
AF:
0.460
Gnomad FIN
AF:
0.289
Gnomad MID
AF:
0.316
Gnomad NFE
AF:
0.253
Gnomad OTH
AF:
0.340
GnomAD3 exomes
AF:
0.324
AC:
81212
AN:
250880
Hom.:
14113
AF XY:
0.323
AC XY:
43792
AN XY:
135650
show subpopulations
Gnomad AFR exome
AF:
0.469
Gnomad AMR exome
AF:
0.395
Gnomad ASJ exome
AF:
0.252
Gnomad EAS exome
AF:
0.339
Gnomad SAS exome
AF:
0.458
Gnomad FIN exome
AF:
0.295
Gnomad NFE exome
AF:
0.256
Gnomad OTH exome
AF:
0.304
GnomAD4 exome
AF:
0.277
AC:
403925
AN:
1460142
Hom.:
59415
AF XY:
0.281
AC XY:
204139
AN XY:
726388
show subpopulations
Gnomad4 AFR exome
AF:
0.463
Gnomad4 AMR exome
AF:
0.390
Gnomad4 ASJ exome
AF:
0.262
Gnomad4 EAS exome
AF:
0.338
Gnomad4 SAS exome
AF:
0.447
Gnomad4 FIN exome
AF:
0.292
Gnomad4 NFE exome
AF:
0.249
Gnomad4 OTH exome
AF:
0.296
GnomAD4 genome
AF:
0.335
AC:
50643
AN:
151364
Hom.:
9153
Cov.:
0
AF XY:
0.341
AC XY:
25216
AN XY:
73908
show subpopulations
Gnomad4 AFR
AF:
0.460
Gnomad4 AMR
AF:
0.358
Gnomad4 ASJ
AF:
0.269
Gnomad4 EAS
AF:
0.359
Gnomad4 SAS
AF:
0.461
Gnomad4 FIN
AF:
0.289
Gnomad4 NFE
AF:
0.253
Gnomad4 OTH
AF:
0.345
Alfa
AF:
0.281
Hom.:
1166
Bravo
AF:
0.343
Asia WGS
AF:
0.490
AC:
1701
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 25, 2013- -
Congenital multicore myopathy with external ophthalmoplegia Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabNov 07, 2021- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 25, 2019- -
King Denborough syndrome Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabNov 07, 2021- -
Central core myopathy Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabNov 07, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs796750554; hg19: chr19-38995355; API