ENST00000675051.1:c.22-4091A>G

Variant names:

• chr7-30594705-A-G
• rs2970504
• ENST00000675051.1:c.22-4091A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000675051.1(GARS1):​c.22-4091A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00968 in 589,932 control chromosomes in the GnomAD database, including 250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (189 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (61 hom.)
• Consequence: GARS1 ENST00000675051.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.164
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 7-30594705-A-G is Benign according to our data. Variant chr7-30594705-A-G is described in ClinVar as Benign. ClinVar VariationId is 359993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000675051.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARS1	NM_002047.4	MANE Select	c.-217A>G		upstream_gene	N/A	NP_002038.2	P41250-1
	GARS1	NM_001316772.1		c.-379A>G		upstream_gene	N/A	NP_001303701.1	P41250-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARS1	ENST00000675051.1		c.22-4091A>G		intron	N/A	ENSP00000502296.1	A0A6Q8PGI6
	GARS1-DT	ENST00000785598.1		n.28T>C		non_coding_transcript_exon	Exon 1 of 1
	GARS1-DT	ENST00000426529.6	TSL:5	n.33+6T>C		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4098 AN: 152092 Hom.: 187 Cov.: 32

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0258

GnomAD4 exome AF: 0.00367 AC: 1605 AN: 437722 Hom.: 61 Cov.: 3 AF XY: 0.00315 AC XY: 727 AN XY: 231094

African (AFR) AF: 0.0972 AC: 1043 AN: 10728

American (AMR) AF: 0.00778 AC: 140 AN: 17986

Ashkenazi Jewish (ASJ) AF: 0.00348 AC: 46 AN: 13200

East Asian (EAS) AF: 0.00 AC: 0 AN: 29402

South Asian (SAS) AF: 0.000244 AC: 11 AN: 45036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29382

Middle Eastern (MID) AF: 0.00569 AC: 11 AN: 1932

European-Non Finnish (NFE) AF: 0.000537 AC: 142 AN: 264618

Other (OTH) AF: 0.00833 AC: 212 AN: 25438

GnomAD4 genome AF: 0.0270 AC: 4105 AN: 152210 Hom.: 189 Cov.: 32 AF XY: 0.0268 AC XY: 1995 AN XY: 74446

African (AFR) AF: 0.0918 AC: 3810 AN: 41518

American (AMR) AF: 0.0122 AC: 187 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 67992

Other (OTH) AF: 0.0256 AC: 54 AN: 2112

Alfa AF: 0.0118 Hom.: 27

Bravo AF: 0.0308

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	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	-0.76
CADD	Benign	5.7
DANN	Benign	0.36
PhyloP100		0.16
PromoterAI		0.11	Neutral
Mutation Taster		=300/0	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: rs2970504; hg19: chr7-30634321;