7-30594853-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The ENST00000675810.1(GARS1):​c.-69T>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00135 in 1,352,650 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 24 hom. )

Consequence

GARS1
ENST00000675810.1 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 4.85
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BP6
Variant 7-30594853-T-A is Benign according to our data. Variant chr7-30594853-T-A is described in ClinVar as [Benign]. Clinvar id is 359998.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00133 (203/152290) while in subpopulation EAS AF= 0.0262 (135/5150). AF 95% confidence interval is 0.0226. There are 4 homozygotes in gnomad4. There are 111 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 203 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GARS1NM_001316772.1 linkuse as main transcriptc.-231T>A 5_prime_UTR_variant 1/17
GARS1NM_002047.4 linkuse as main transcript upstream_gene_variant ENST00000389266.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GARS1ENST00000389266.8 linkuse as main transcript upstream_gene_variant 1 NM_002047.4 P2P41250-1

Frequencies

GnomAD3 genomes
AF:
0.00133
AC:
203
AN:
152172
Hom.:
4
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00301
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0262
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.000478
GnomAD4 exome
AF:
0.00135
AC:
1626
AN:
1200360
Hom.:
24
Cov.:
17
AF XY:
0.00131
AC XY:
784
AN XY:
600336
show subpopulations
Gnomad4 AFR exome
AF:
0.0000367
Gnomad4 AMR exome
AF:
0.00770
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0362
Gnomad4 SAS exome
AF:
0.0000670
Gnomad4 FIN exome
AF:
0.000177
Gnomad4 NFE exome
AF:
0.0000741
Gnomad4 OTH exome
AF:
0.000892
GnomAD4 genome
AF:
0.00133
AC:
203
AN:
152290
Hom.:
4
Cov.:
33
AF XY:
0.00149
AC XY:
111
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.00300
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0262
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000106
Hom.:
0
Bravo
AF:
0.00189
Asia WGS
AF:
0.00924
AC:
32
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Distal spinal muscular atrophy Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 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. -
Charcot-Marie-Tooth disease type 2D Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 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 13, 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
-0.23
CADD
Benign
19
DANN
Benign
0.94

Splicing

Name
Calibrated prediction
Score
Prediction
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs527307703; hg19: chr7-30634469; API