GeneBe

7-30595148-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002047.4(GARS1):​c.222+5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

GARS1
NM_002047.4 splice_region, intron

Scores

2
Splicing: ADA: 0.00008123
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00800

Publications

0 publications found
Variant links:
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-DT (HGNC:48951): (GARS1 divergent transcript)

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=-0.55).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GARS1NM_002047.4 linkc.222+5C>G splice_region_variant, intron_variant Intron 1 of 16 ENST00000389266.8 NP_002038.2 P41250-1
GARS1NM_001316772.1 linkc.60+5C>G splice_region_variant, intron_variant Intron 1 of 16 NP_001303701.1 P41250-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GARS1ENST00000389266.8 linkc.222+5C>G splice_region_variant, intron_variant Intron 1 of 16 1 NM_002047.4 ENSP00000373918.3 P41250-1
GARS1ENST00000675651.1 linkc.222+5C>G splice_region_variant, intron_variant Intron 1 of 16 ENSP00000502513.1 A0A6Q8PGZ8
GARS1ENST00000675810.1 linkc.222+5C>G splice_region_variant, intron_variant Intron 1 of 15 ENSP00000502743.1 A0A6Q8PHH9
GARS1ENST00000675693.1 linkc.54+5C>G splice_region_variant, intron_variant Intron 2 of 17 ENSP00000502174.1 A0A6Q8PGA8
GARS1ENST00000675051.1 linkc.22-3648C>G intron_variant Intron 1 of 16 ENSP00000502296.1 A0A6Q8PGI6
GARS1ENST00000674815.1 linkc.-148+196C>G intron_variant Intron 1 of 16 ENSP00000502799.1 A0A6Q8PGW4
GARS1ENST00000674851.1 linkc.-148+5C>G splice_region_variant, intron_variant Intron 2 of 17 ENSP00000502451.1 A0A6Q8PGW4
GARS1ENST00000444666.6 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 17 3 ENSP00000415447.2 H7C443
GARS1ENST00000674616.1 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 17 ENSP00000502408.1 A0A6Q8PGT3
GARS1ENST00000674643.1 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 16 ENSP00000501636.1 A0A6Q8PF45
GARS1ENST00000674737.1 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 17 ENSP00000502464.1 A0A6Q8PGZ9
GARS1ENST00000674807.1 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 15 ENSP00000502814.1 A0A6Q8PFZ6
GARS1ENST00000675529.1 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 17 ENSP00000501655.1 A0A6Q8PFN0
GARS1ENST00000675859.1 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 14 ENSP00000502033.1 A0A6Q8PFZ6
GARS1ENST00000676088.1 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 18 ENSP00000501884.1 A0A6Q8PFN0
GARS1ENST00000676140.1 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 16 ENSP00000502571.1 A0A6Q8PH49
GARS1ENST00000676164.1 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 16 ENSP00000501986.1 A0A6Q8PFV5
GARS1ENST00000676210.1 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 17 ENSP00000502373.1 A0A6Q8PGN7
GARS1ENST00000676259.1 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 16 ENSP00000501980.1 A0A6Q8PFU7
GARS1ENST00000676403.1 linkn.222+5C>G splice_region_variant, intron_variant Intron 1 of 15 ENSP00000502681.1 A0A6Q8PHI7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.23e-7
AC:
1
AN:
1383866
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
683002
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31586
American (AMR)
AF:
0.00
AC:
0
AN:
35714
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25168
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35772
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79208
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34752
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5628
European-Non Finnish (NFE)
AF:
9.27e-7
AC:
1
AN:
1078170
Other (OTH)
AF:
0.00
AC:
0
AN:
57868
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
13
DANN
Benign
0.85
PhyloP100
0.0080
PromoterAI
0.11
Neutral

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000081
dbscSNV1_RF
Benign
0.0080
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

Other links and lift over

dbSNP: rs2072236; hg19: chr7-30634764; API