rs39739

Positions:

• chr7-30585975-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000675051.1(GARS1):​c.21+5385C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 152,362 control chromosomes in the GnomAD database, including 535 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.073 (534 hom., cov: 33)
  • Exomes 𝑓: 0.091 (1 hom.)
• Consequence: GARS1 ENST00000675051.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.30585975C>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000675051.1	c.21+5385C>A		intron_variant				ENSP00000502296.1

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11172 AN: 152178 Hom.: 532 Cov.: 33

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0909 AC: 6 AN: 66 Hom.: 1 Cov.: 0 AF XY: 0.0577 AC XY: 3 AN XY: 52

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0734 AC: 11176 AN: 152296 Hom.: 534 Cov.: 33 AF XY: 0.0754 AC XY: 5617 AN XY: 74470

Gnomad4 AFR AF: 0.0379

Gnomad4 AMR AF: 0.0758

Gnomad4 ASJ AF: 0.0901

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.0585

Gnomad4 NFE AF: 0.0790

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0704 Hom.: 51

Bravo AF: 0.0725

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs39739; hg19: chr7-30625591;