19-38442305-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000540.3(RYR1):​c.166-44G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,300,852 control chromosomes in the GnomAD database, including 196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 122 hom., cov: 30)
Exomes 𝑓: 0.0023 ( 74 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0640
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BP6
Variant 19-38442305-G-C is Benign according to our data. Variant chr19-38442305-G-C is described in ClinVar as [Benign]. Clinvar id is 256461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0692 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RYR1NM_000540.3 linkc.166-44G>C intron_variant Intron 2 of 105 ENST00000359596.8 NP_000531.2 P21817-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RYR1ENST00000359596.8 linkc.166-44G>C intron_variant Intron 2 of 105 5 NM_000540.3 ENSP00000352608.2 P21817-1
RYR1ENST00000355481.8 linkc.166-44G>C intron_variant Intron 2 of 104 1 ENSP00000347667.3 P21817-2
RYR1ENST00000599547.6 linkn.166-44G>C intron_variant Intron 2 of 79 2 ENSP00000471601.2 M0R127

Frequencies

GnomAD3 genomes
AF:
0.0206
AC:
3119
AN:
151340
Hom.:
121
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0715
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00808
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000417
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000339
Gnomad OTH
AF:
0.0139
GnomAD3 exomes
AF:
0.00566
AC:
1410
AN:
248992
Hom.:
56
AF XY:
0.00412
AC XY:
555
AN XY:
134750
show subpopulations
Gnomad AFR exome
AF:
0.0738
Gnomad AMR exome
AF:
0.00444
Gnomad ASJ exome
AF:
0.00312
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000188
Gnomad OTH exome
AF:
0.00313
GnomAD4 exome
AF:
0.00231
AC:
2650
AN:
1149398
Hom.:
74
Cov.:
16
AF XY:
0.00194
AC XY:
1140
AN XY:
586870
show subpopulations
Gnomad4 AFR exome
AF:
0.0695
Gnomad4 AMR exome
AF:
0.00517
Gnomad4 ASJ exome
AF:
0.00344
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000999
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000177
Gnomad4 OTH exome
AF:
0.00543
GnomAD4 genome
AF:
0.0206
AC:
3122
AN:
151454
Hom.:
122
Cov.:
30
AF XY:
0.0201
AC XY:
1486
AN XY:
74036
show subpopulations
Gnomad4 AFR
AF:
0.0714
Gnomad4 AMR
AF:
0.00807
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000418
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000339
Gnomad4 OTH
AF:
0.0138
Alfa
AF:
0.00135
Hom.:
0
Bravo
AF:
0.0228
Asia WGS
AF:
0.00404
AC:
14
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jul 09, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:1
Oct 17, 2013
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.28
DANN
Benign
0.42

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: rs115526671; hg19: chr19-38932945; API