rs768090444
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_000070.3(CAPN3):c.2242C>A(p.Arg748Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000684 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
CAPN3
NM_000070.3 synonymous
NM_000070.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.21
Publications
0 publications found
Genes affected
CAPN3 (HGNC:1480): (calpain 3) Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene encodes a muscle-specific member of the calpain large subunit family that specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed. [provided by RefSeq, Jul 2008]
CAPN3 Gene-Disease associations (from GenCC):
- autosomal recessive limb-girdle muscular dystrophyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- autosomal recessive limb-girdle muscular dystrophy type 2AInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
- muscular dystrophy, limb-girdle, autosomal dominant 4Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- muscular dystrophy, limb-girdle, autosomal dominantInheritance: AD Classification: LIMITED Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 15-42410645-C-A is Benign according to our data. Variant chr15-42410645-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1153339.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CAPN3 | ENST00000397163.8 | c.2242C>A | p.Arg748Arg | synonymous_variant | Exon 21 of 24 | 1 | NM_000070.3 | ENSP00000380349.3 | ||
| CAPN3 | ENST00000673886.1 | c.247C>A | p.Arg83Arg | synonymous_variant | Exon 8 of 11 | ENSP00000501155.1 | ||||
| CAPN3 | ENST00000673928.1 | c.247C>A | p.Arg83Arg | synonymous_variant | Exon 8 of 11 | ENSP00000501099.1 | ||||
| CAPN3 | ENST00000674146.1 | c.247C>A | p.Arg83Arg | synonymous_variant | Exon 9 of 12 | ENSP00000501175.1 | ||||
| CAPN3 | ENST00000674149.1 | c.247C>A | p.Arg83Arg | synonymous_variant | Exon 8 of 11 | ENSP00000501112.1 | ||||
| CAPN3 | ENST00000673743.1 | c.145C>A | p.Arg49Arg | synonymous_variant | Exon 8 of 11 | ENSP00000500989.1 | ||||
| ENSG00000258461 | ENST00000495723.1 | n.*2678C>A | non_coding_transcript_exon_variant | Exon 23 of 26 | 2 | ENSP00000492063.1 | ||||
| ENSG00000258461 | ENST00000495723.1 | n.*2678C>A | 3_prime_UTR_variant | Exon 23 of 26 | 2 | ENSP00000492063.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461646Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727120 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461646
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727120
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44680
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26130
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86236
European-Finnish (FIN)
AF:
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111854
Other (OTH)
AF:
AC:
0
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2A Benign:1
Dec 10, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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