7-30616026-C-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_002047.4(GARS1):c.1162C>A(p.Arg388Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000657 in 152,120 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
GARS1
NM_002047.4 synonymous
NM_002047.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.97
Publications
3 publications found
Genes affected
GARS1 (HGNC:4162): (glycyl-tRNA synthetase 1) This gene encodes glycyl-tRNA synthetase, one of the aminoacyl-tRNA synthetases that charge tRNAs with their cognate amino acids. The encoded enzyme is an (alpha)2 dimer which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
GARS1 Gene-Disease associations (from GenCC):
- Charcot-Marie-Tooth disease type 2DInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
- neuronopathy, distal hereditary motor, type 5AInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, Laboratory for Molecular Medicine
- spinal muscular atrophy, infantile, James typeInheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
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=-0.25).
BP6
Variant 7-30616026-C-A is Benign according to our data. Variant chr7-30616026-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1082265.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_002047.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GARS1 | NM_002047.4 | MANE Select | c.1162C>A | p.Arg388Arg | synonymous | Exon 9 of 17 | NP_002038.2 | ||
| GARS1 | NM_001316772.1 | c.1000C>A | p.Arg334Arg | synonymous | Exon 9 of 17 | NP_001303701.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GARS1 | ENST00000389266.8 | TSL:1 MANE Select | c.1162C>A | p.Arg388Arg | synonymous | Exon 9 of 17 | ENSP00000373918.3 | ||
| GARS1 | ENST00000675651.1 | c.1162C>A | p.Arg388Arg | synonymous | Exon 9 of 17 | ENSP00000502513.1 | |||
| GARS1 | ENST00000675810.1 | c.1060C>A | p.Arg354Arg | synonymous | Exon 8 of 16 | ENSP00000502743.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152120
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74318 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
152120
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74318
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
41416
American (AMR)
AF:
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68030
Other (OTH)
AF:
AC:
0
AN:
2090
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Benign:1
Mar 25, 2021
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
RBP_binding_hub_radar
RBP_regulation_power_radar
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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.