7-30595014-G-C

Variant names:

• chr7-30595014-G-C
• rs2529438
• NM_002047.4:c.93G>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002047.4(GARS1):​c.93G>C​(p.Leu31Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 1,580,278 control chromosomes in the GnomAD database, including 8,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L31L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.10 (875 hom., cov: 33)
  • Exomes 𝑓: 0.098 (7881 hom.)
• Consequence: GARS1 NM_002047.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.670
• Publications: 20 publications found

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:48951): (GARS1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-30595014-G-C is Benign according to our data. Variant chr7-30595014-G-C is described in ClinVar as Benign. ClinVar VariationId is 137444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.67 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002047.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARS1	NM_002047.4	MANE Select	c.93G>C	p.Leu31Leu	synonymous	Exon 1 of 17	NP_002038.2
	GARS1	NM_001316772.1		c.-70G>C		5_prime_UTR	Exon 1 of 17	NP_001303701.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARS1	ENST00000389266.8	TSL:1 MANE Select	c.93G>C	p.Leu31Leu	synonymous	Exon 1 of 17	ENSP00000373918.3
	GARS1	ENST00000675651.1		c.93G>C	p.Leu31Leu	synonymous	Exon 1 of 17	ENSP00000502513.1
	GARS1	ENST00000675810.1		c.93G>C	p.Leu31Leu	synonymous	Exon 1 of 16	ENSP00000502743.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15532 AN: 152104 Hom.: 873 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0935

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0612

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.128

GnomAD2 exomes AF: 0.111 AC: 21591 AN: 194036 AF XY: 0.115

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.0752

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.161

Gnomad FIN exome AF: 0.0635

Gnomad NFE exome AF: 0.0936

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.0982 AC: 140215 AN: 1428056 Hom.: 7881 Cov.: 31 AF XY: 0.101 AC XY: 71417 AN XY: 709156

African (AFR) AF: 0.119 AC: 3931 AN: 33054

American (AMR) AF: 0.0768 AC: 3264 AN: 42496

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2860 AN: 25688

East Asian (EAS) AF: 0.191 AC: 7389 AN: 38626

South Asian (SAS) AF: 0.188 AC: 15611 AN: 83158

European-Finnish (FIN) AF: 0.0626 AC: 2334 AN: 37258

Middle Eastern (MID) AF: 0.149 AC: 821 AN: 5496

European-Non Finnish (NFE) AF: 0.0884 AC: 97487 AN: 1102874

Other (OTH) AF: 0.110 AC: 6518 AN: 59406

GnomAD4 genome AF: 0.102 AC: 15542 AN: 152222 Hom.: 875 Cov.: 33 AF XY: 0.103 AC XY: 7653 AN XY: 74432

African (AFR) AF: 0.119 AC: 4938 AN: 41528

American (AMR) AF: 0.0934 AC: 1429 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3468

East Asian (EAS) AF: 0.179 AC: 922 AN: 5156

South Asian (SAS) AF: 0.199 AC: 961 AN: 4830

European-Finnish (FIN) AF: 0.0612 AC: 650 AN: 10618

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0877 AC: 5967 AN: 68000

Other (OTH) AF: 0.132 AC: 279 AN: 2116

Alfa AF: 0.0656 Hom.: 119

Bravo AF: 0.106

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	Charcot-Marie-Tooth disease type 2 (1)
-	-	1	Charcot-Marie-Tooth disease type 2D (1)
-	-	1	Distal spinal muscular atrophy (1)
-	-	1	Neuronopathy, distal hereditary motor, type 5A (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.58
PhyloP100		0.67
PromoterAI		0.0081	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2529438; hg19: chr7-30634630; COSMIC: COSV66828729; COSMIC: COSV66828729;