rs2527878
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002047.4(GARS1):c.1032-23A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0973 in 1,613,316 control chromosomes in the GnomAD database, including 8,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.10 ( 867 hom., cov: 33)
Exomes 𝑓: 0.097 ( 7956 hom. )
Consequence
GARS1
NM_002047.4 intron
NM_002047.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.148
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 7-30615873-A-T is Benign according to our data. Variant chr7-30615873-A-T is described in ClinVar as [Benign]. Clinvar id is 258531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-30615873-A-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GARS1 | NM_002047.4 | c.1032-23A>T | intron_variant | ENST00000389266.8 | NP_002038.2 | |||
GARS1 | NM_001316772.1 | c.870-23A>T | intron_variant | NP_001303701.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GARS1 | ENST00000389266.8 | c.1032-23A>T | intron_variant | 1 | NM_002047.4 | ENSP00000373918.3 | ||||
GARS1 | ENST00000675651.1 | c.1032-23A>T | intron_variant | ENSP00000502513.1 | ||||||
GARS1 | ENST00000675810.1 | c.930-23A>T | intron_variant | ENSP00000502743.1 | ||||||
GARS1 | ENST00000675693.1 | c.864-23A>T | intron_variant | ENSP00000502174.1 | ||||||
GARS1 | ENST00000675051.1 | c.831-23A>T | intron_variant | ENSP00000502296.1 | ||||||
GARS1 | ENST00000674815.1 | c.663-23A>T | intron_variant | ENSP00000502799.1 | ||||||
GARS1 | ENST00000674851.1 | c.663-23A>T | intron_variant | ENSP00000502451.1 | ||||||
GARS1 | ENST00000444666.6 | n.1032-23A>T | intron_variant | 3 | ENSP00000415447.2 | |||||
GARS1 | ENST00000674616.1 | n.*746-23A>T | intron_variant | ENSP00000502408.1 | ||||||
GARS1 | ENST00000674643.1 | n.*132-23A>T | intron_variant | ENSP00000501636.1 | ||||||
GARS1 | ENST00000674737.1 | n.*370-23A>T | intron_variant | ENSP00000502464.1 | ||||||
GARS1 | ENST00000674807.1 | n.1032-23A>T | intron_variant | ENSP00000502814.1 | ||||||
GARS1 | ENST00000675529.1 | n.*902-23A>T | intron_variant | ENSP00000501655.1 | ||||||
GARS1 | ENST00000675859.1 | n.1032-23A>T | intron_variant | ENSP00000502033.1 | ||||||
GARS1 | ENST00000676088.1 | n.*974-23A>T | intron_variant | ENSP00000501884.1 | ||||||
GARS1 | ENST00000676140.1 | n.1032-25A>T | intron_variant | ENSP00000502571.1 | ||||||
GARS1 | ENST00000676164.1 | n.*483-23A>T | intron_variant | ENSP00000501986.1 | ||||||
GARS1 | ENST00000676210.1 | n.*321-23A>T | intron_variant | ENSP00000502373.1 | ||||||
GARS1 | ENST00000676259.1 | n.*464-23A>T | intron_variant | ENSP00000501980.1 | ||||||
GARS1 | ENST00000676403.1 | n.1032-23A>T | intron_variant | ENSP00000502681.1 |
Frequencies
GnomAD3 genomes AF: 0.101 AC: 15373AN: 152088Hom.: 865 Cov.: 33
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GnomAD3 exomes AF: 0.107 AC: 26655AN: 249006Hom.: 1702 AF XY: 0.111 AC XY: 14967AN XY: 135138
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GnomAD4 exome AF: 0.0969 AC: 141647AN: 1461110Hom.: 7956 Cov.: 31 AF XY: 0.0996 AC XY: 72413AN XY: 726854
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GnomAD4 genome AF: 0.101 AC: 15382AN: 152206Hom.: 867 Cov.: 33 AF XY: 0.102 AC XY: 7585AN XY: 74414
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
La Branchor
BranchPoint Hunter
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at