rs1558064

chr7-30603453-C-Achr7-30603453-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002047.4(GARS1):c.659-43C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,482,540 control chromosomes in the GnomAD database, including 277,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (21416 hom., cov: 32)
  • Exomes 𝑓: 0.61 (255973 hom.)
• Consequence: GARS1 NM_002047.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.151

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-30603453-C-A is Benign according to our data. Variant chr7-30603453-C-A is described in ClinVar as [Benign]. Clinvar id is 258537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GARS1	NM_002047.4	c.659-43C>A		intron_variant		ENST00000389266.8
GARS1	NM_001316772.1	c.497-43C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GARS1	ENST00000389266.8	c.659-43C>A		intron_variant		1	NM_002047.4	P2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73395 AN: 151924 Hom.: 21419 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.514

GnomAD3 exomes AF: 0.559 AC: 138079 AN: 246982 Hom.: 41015 AF XY: 0.561 AC XY: 75252 AN XY: 134036

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.557

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.488

Gnomad SAS exome AF: 0.416

Gnomad FIN exome AF: 0.638

Gnomad NFE exome AF: 0.643

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.611 AC: 812985 AN: 1330496 Hom.: 255973 Cov.: 20 AF XY: 0.606 AC XY: 405808 AN XY: 669240

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.552

Gnomad4 ASJ exome AF: 0.669

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.638

Gnomad4 NFE exome AF: 0.650

Gnomad4 OTH exome AF: 0.579

GnomAD4 genome AF: 0.483 AC: 73392 AN: 152044 Hom.: 21416 Cov.: 32 AF XY: 0.481 AC XY: 35713 AN XY: 74292

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.512

Alfa AF: 0.525 Hom.: 3357

Bravo AF: 0.460

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Spinal muscular atrophy, infantile, James type Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Neuronopathy, distal hereditary motor, type 5A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Charcot-Marie-Tooth disease type 2D Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.1
Dann	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1558064; hg19: chr7-30643069; COSMIC: COSV66828323; COSMIC: COSV66828323;