rs202117737

Variant names:

• chr7-30594972-G-A
• rs202117737
• NM_002047.4:c.51G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000389266.8(GARS1):​c.51G>A​(p.Leu17Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,595,148 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: GARS1 ENST00000389266.8 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.08
• Publications: 1 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=-0.77).
• BP6: Variant 7-30594972-G-A is Benign according to our data. Variant chr7-30594972-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 416090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.08 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000217 (33/152288) while in subpopulation AMR AF = 0.00209 (32/15308). AF 95% confidence interval is 0.00152. There are 1 homozygotes in GnomAd4. There are 15 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 33 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000389266.8. 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.51G>A	p.Leu17Leu	synonymous	Exon 1 of 17	NP_002038.2
	GARS1	NM_001316772.1		c.-112G>A		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.51G>A	p.Leu17Leu	synonymous	Exon 1 of 17	ENSP00000373918.3
	GARS1	ENST00000675651.1		c.51G>A	p.Leu17Leu	synonymous	Exon 1 of 17	ENSP00000502513.1
	GARS1	ENST00000675810.1		c.51G>A	p.Leu17Leu	synonymous	Exon 1 of 16	ENSP00000502743.1

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152170 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

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: 0.000478

GnomAD2 exomes AF: 0.00123 AC: 269 AN: 218476 AF XY: 0.00102

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00781

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00127

GnomAD4 exome AF: 0.000215 AC: 310 AN: 1442860 Hom.: 1 Cov.: 30 AF XY: 0.000195 AC XY: 140 AN XY: 717956

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.00682 AC: 302 AN: 44310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25992

East Asian (EAS) AF: 0.00 AC: 0 AN: 39540

South Asian (SAS) AF: 0.00 AC: 0 AN: 85278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5178

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110144

Other (OTH) AF: 0.000133 AC: 8 AN: 59956

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152288 Hom.: 1 Cov.: 33 AF XY: 0.000201 AC XY: 15 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.00209 AC: 32 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000268 Hom.: 0

Bravo AF: 0.000650

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Charcot-Marie-Tooth disease type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.6
DANN	Benign	0.86
PhyloP100		1.1
PromoterAI		0.0067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs202117737; hg19: chr7-30634588;