chr7-30594605-G-A

Variant summary

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

The ENST00000675051.1(GARS1):​c.22-4191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00661 in 455,268 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 55 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 10 hom. )

Consequence

GARS1
ENST00000675051.1 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0780
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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 7-30594605-G-A is Benign according to our data. Variant chr7-30594605-G-A is described in ClinVar as [Benign]. Clinvar id is 359990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GARS1ENST00000675051.1 linkuse as main transcriptc.22-4191G>A intron_variant
GARS1-DTENST00000426529.6 linkuse as main transcriptn.33+106C>T intron_variant, non_coding_transcript_variant 5
GARS1-DTENST00000578994.5 linkuse as main transcriptn.99+106C>T intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.0159
AC:
2415
AN:
152176
Hom.:
54
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0545
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00569
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000470
Gnomad OTH
AF:
0.0167
GnomAD4 exome
AF:
0.00194
AC:
588
AN:
302974
Hom.:
10
AF XY:
0.00162
AC XY:
257
AN XY:
158584
show subpopulations
Gnomad4 AFR exome
AF:
0.0558
Gnomad4 AMR exome
AF:
0.00385
Gnomad4 ASJ exome
AF:
0.000208
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000384
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000446
Gnomad4 OTH exome
AF:
0.00481
GnomAD4 genome
AF:
0.0159
AC:
2420
AN:
152294
Hom.:
55
Cov.:
32
AF XY:
0.0155
AC XY:
1155
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0545
Gnomad4 AMR
AF:
0.00562
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000470
Gnomad4 OTH
AF:
0.0166
Alfa
AF:
0.0124
Hom.:
9
Bravo
AF:
0.0181
Asia WGS
AF:
0.00433
AC:
15
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Distal spinal muscular atrophy Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018This 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. -
Charcot-Marie-Tooth disease type 2D Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Neuronopathy, distal hereditary motor, type 5A Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
3.8
DANN
Benign
0.78
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

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: rs116125961; hg19: chr7-30634221; API