Variant rs118002895 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002047.4(GARS1):c.1700-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 1,325,674 control chromosomes in the GnomAD database, including 664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 75 hom., cov: 32)

Exomes 𝑓: 0.029 ( 589 hom. )

Consequence

GARS1
NM_002047.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.626

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 7-30628515-T-C is Benign according to our data. Variant chr7-30628515-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 258533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-30628515-T-C is described in Lovd as [Benign]. Variant chr7-30628515-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0226 (3441/152330) while in subpopulation NFE AF= 0.0323 (2196/68028). AF 95% confidence interval is 0.0312. There are 75 homozygotes in gnomad4. There are 1718 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3441 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARS1	NM_002047.4 linkuse as main transcript	c.1700-45T>C		intron_variant		ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1 linkuse as main transcript	c.1538-45T>C		intron_variant			NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000389266.8 linkuse as main transcript	c.1700-45T>C		intron_variant		1	NM_002047.4	ENSP00000373918	P2	P41250-1

Frequencies

GnomAD3 genomes

AF:

0.0226

AC:

3443

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00417

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.0598

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.0244

AC:

6089

AN:

249392

Hom.:

131

AF XY:

0.0250

AC XY:

3383

AN XY:

135302

show subpopulations

Gnomad AFR exome

AF:

0.00459

Gnomad AMR exome

AF:

0.00964

Gnomad ASJ exome

AF:

0.0249

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0172

Gnomad FIN exome

AF:

0.0551

Gnomad NFE exome

AF:

0.0317

Gnomad OTH exome

AF:

0.0213

GnomAD4 exome

AF:

0.0289

AC:

33960

AN:

1173344

Hom.:

589

Cov.:

AF XY:

0.0290

AC XY:

17339

AN XY:

598030

show subpopulations

Gnomad4 AFR exome

AF:

0.00405

Gnomad4 AMR exome

AF:

0.00957

Gnomad4 ASJ exome

AF:

0.0268

Gnomad4 EAS exome

AF:

0.0000530

Gnomad4 SAS exome

AF:

0.0186

Gnomad4 FIN exome

AF:

0.0530

Gnomad4 NFE exome

AF:

0.0318

Gnomad4 OTH exome

AF:

0.0263

GnomAD4 genome

AF:

0.0226

AC:

3441

AN:

152330

Hom.:

Cov.:

AF XY:

0.0231

AC XY:

1718

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00416

Gnomad4 AMR

AF:

0.0120

Gnomad4 ASJ

AF:

0.0239

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0137

Gnomad4 FIN

AF:

0.0598

Gnomad4 NFE

AF:

0.0323

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0296

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.5

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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