rs1558064

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.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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.151

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 links:

GARS1 (HGNC:):

GARS1 links:

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=-0.82).

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	Protein	UniProt
GARS1	NM_002047.4 linkuse as main transcript	c.659-43C>A		intron_variant		ENST00000389266.8	NP_002038.2	P41250-1
GARS1	NM_001316772.1 linkuse as main transcript	c.497-43C>A		intron_variant			NP_001303701.1	P41250-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
GARS1	ENST00000389266.8 linkuse as main transcript	c.659-43C>A	intron_variant	1	NM_002047.4	ENSP00000373918.3	P41250-1
GARS1	ENST00000675651.1 linkuse as main transcript	c.659-43C>A	intron_variant			ENSP00000502513.1	A0A6Q8PGZ8
GARS1	ENST00000675810.1 linkuse as main transcript	c.557-43C>A	intron_variant			ENSP00000502743.1	A0A6Q8PHH9
GARS1	ENST00000675693.1 linkuse as main transcript	c.491-43C>A	intron_variant			ENSP00000502174.1	A0A6Q8PGA8
GARS1	ENST00000675051.1 linkuse as main transcript	c.458-43C>A	intron_variant			ENSP00000502296.1	A0A6Q8PGI6
GARS1	ENST00000674815.1 linkuse as main transcript	c.290-43C>A	intron_variant			ENSP00000502799.1	A0A6Q8PGW4
GARS1	ENST00000674851.1 linkuse as main transcript	c.290-43C>A	intron_variant			ENSP00000502451.1	A0A6Q8PGW4
GARS1	ENST00000444666.6 linkuse as main transcript	n.659-43C>A	intron_variant	3		ENSP00000415447.2	H7C443
GARS1	ENST00000674616.1 linkuse as main transcript	n.*373-43C>A	intron_variant			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 linkuse as main transcript	n.659-43C>A	intron_variant			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 linkuse as main transcript	n.659-43C>A	intron_variant			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 linkuse as main transcript	n.659-43C>A	intron_variant			ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 linkuse as main transcript	n.*529-43C>A	intron_variant			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 linkuse as main transcript	n.659-43C>A	intron_variant			ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 linkuse as main transcript	n.*529-43C>A	intron_variant			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 linkuse as main transcript	n.659-43C>A	intron_variant			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676164.1 linkuse as main transcript	n.*110-43C>A	intron_variant			ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 linkuse as main transcript	n.659-43C>A	intron_variant			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 linkuse as main transcript	n.*91-43C>A	intron_variant			ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 linkuse as main transcript	n.659-43C>A	intron_variant			ENSP00000502681.1	A0A6Q8PHI7

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73395

AN:

151924

Hom.:

21419

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.606

AC XY:

405808

AN XY:

669240

show subpopulations

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.:

AF XY:

0.481

AC XY:

35713

AN XY:

74292

show subpopulations

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

LINK: link

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

- -

Charcot-Marie-Tooth disease type 2D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Neuronopathy, distal hereditary motor, type 5A

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over