7-30594697-G-A

Variant names:

• chr7-30594697-G-A
• rs148593022
• ENST00000675051.1:c.22-4099G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000675051.1(GARS1):​c.22-4099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00784 in 582,142 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (10 hom., cov: 33)
  • Exomes 𝑓: 0.0084 (19 hom.)
• Consequence: GARS1 ENST00000675051.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.02
• Publications: 0 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=-0.77).
• BP6: Variant 7-30594697-G-A is Benign according to our data. Variant chr7-30594697-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 359992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00629 (958/152292) while in subpopulation NFE AF = 0.01 (682/68016). AF 95% confidence interval is 0.0094. There are 10 homozygotes in GnomAd4. There are 459 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 958 AD gene.

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.-225G>A		upstream_gene	N/A	NP_002038.2	P41250-1
	GARS1	NM_001316772.1		c.-387G>A		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.22-4099G>A		intron	N/A	ENSP00000502296.1	A0A6Q8PGI6
	GARS1-DT	ENST00000785598.1		n.36C>T		non_coding_transcript_exon	Exon 1 of 1
	GARS1-DT	ENST00000426529.6	TSL:5	n.33+14C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00630 AC: 958 AN: 152174 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00763

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.00838 AC: 3604 AN: 429850 Hom.: 19 Cov.: 3 AF XY: 0.00803 AC XY: 1819 AN XY: 226470

African (AFR) AF: 0.00215 AC: 22 AN: 10234

American (AMR) AF: 0.00289 AC: 50 AN: 17278

Ashkenazi Jewish (ASJ) AF: 0.00657 AC: 85 AN: 12946

East Asian (EAS) AF: 0.00 AC: 0 AN: 28742

South Asian (SAS) AF: 0.00190 AC: 84 AN: 44300

European-Finnish (FIN) AF: 0.00845 AC: 247 AN: 29214

Middle Eastern (MID) AF: 0.000525 AC: 1 AN: 1904

European-Non Finnish (NFE) AF: 0.0112 AC: 2915 AN: 260138

Other (OTH) AF: 0.00797 AC: 200 AN: 25094

GnomAD4 genome AF: 0.00629 AC: 958 AN: 152292 Hom.: 10 Cov.: 33 AF XY: 0.00616 AC XY: 459 AN XY: 74456

African (AFR) AF: 0.00202 AC: 84 AN: 41560

American (AMR) AF: 0.00438 AC: 67 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4822

European-Finnish (FIN) AF: 0.00763 AC: 81 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0100 AC: 682 AN: 68016

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00900 Hom.: 1

Bravo AF: 0.00592

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.77
CADD	Benign	4.6
DANN	Benign	0.77
PhyloP100		1.0
PromoterAI		0.018	Neutral
Mutation Taster		=300/0	polymorphism

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: rs148593022; hg19: chr7-30634313;