rs2240401

Positions:

• chr7-30633729-C-G
• chr7-30633729-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002047.4(GARS1):​c.2095-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: GARS1 NM_002047.4 splice_region, intron
• Scores: Splicing: ADA: 0.00008648
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARS1	NM_002047.4	c.2095-6C>G		splice_region_variant, intron_variant		ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1	c.1933-6C>G		splice_region_variant, intron_variant			NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000389266.8	c.2095-6C>G		splice_region_variant, intron_variant		1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.2113-6C>G		splice_region_variant, intron_variant				ENSP00000502513.1
GARS1	ENST00000675810.1	c.1993-6C>G		splice_region_variant, intron_variant				ENSP00000502743.1
GARS1	ENST00000675693.1	c.1927-6C>G		splice_region_variant, intron_variant				ENSP00000502174.1
GARS1	ENST00000675051.1	c.1894-6C>G		splice_region_variant, intron_variant				ENSP00000502296.1
GARS1	ENST00000674815.1	c.1726-6C>G		splice_region_variant, intron_variant				ENSP00000502799.1
GARS1	ENST00000674851.1	c.1726-6C>G		splice_region_variant, intron_variant				ENSP00000502451.1
GARS1	ENST00000444666.6	n.*516-6C>G		splice_region_variant, intron_variant		3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.*1809-6C>G		splice_region_variant, intron_variant				ENSP00000502408.1
GARS1	ENST00000674643.1	n.*1900-6C>G		splice_region_variant, intron_variant				ENSP00000501636.1
GARS1	ENST00000674737.1	n.*1433-6C>G		splice_region_variant, intron_variant				ENSP00000502464.1
GARS1	ENST00000674807.1	n.*368-6C>G		splice_region_variant, intron_variant				ENSP00000502814.1
GARS1	ENST00000675529.1	n.*1965-6C>G		splice_region_variant, intron_variant				ENSP00000501655.1
GARS1	ENST00000675859.1	n.*274-6C>G		splice_region_variant, intron_variant				ENSP00000502033.1
GARS1	ENST00000676088.1	n.*2037-6C>G		splice_region_variant, intron_variant				ENSP00000501884.1
GARS1	ENST00000676140.1	n.*1040-6C>G		splice_region_variant, intron_variant				ENSP00000502571.1
GARS1	ENST00000676164.1	n.*1546-6C>G		splice_region_variant, intron_variant				ENSP00000501986.1
GARS1	ENST00000676210.1	n.*1384-6C>G		splice_region_variant, intron_variant				ENSP00000502373.1
GARS1	ENST00000676259.1	n.*1527-6C>G		splice_region_variant, intron_variant				ENSP00000501980.1
GARS1	ENST00000676403.1	n.*180-6C>G		splice_region_variant, intron_variant				ENSP00000502681.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151836 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 42

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151836 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74118

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000086
dbscSNV1_RF	Benign	0.10
SpliceAI score (max)		0.010		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: rs2240401; hg19: chr7-30673345;