ENST00000675051.1:c.22-4079C>T

Variant names:

• chr7-30594717-C-T
• rs17159262
• ENST00000675051.1:c.22-4079C>T

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.22-4079C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 596,034 control chromosomes in the GnomAD database, including 220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (77 hom., cov: 33)
  • Exomes 𝑓: 0.024 (143 hom.)
• Consequence: GARS1 ENST00000675051.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.05
• Publications: 3 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=-0.75).
• BP6: Variant 7-30594717-C-T is Benign according to our data. Variant chr7-30594717-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 359994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0287 (4378/152320) while in subpopulation AFR AF = 0.0343 (1427/41568). AF 95% confidence interval is 0.0328. There are 77 homozygotes in GnomAd4. There are 2041 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4378 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.-205C>T		upstream_gene	N/A	NP_002038.2	P41250-1
	GARS1	NM_001316772.1		c.-367C>T		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.22-4079C>T		intron	N/A	ENSP00000502296.1	A0A6Q8PGI6
	GARS1-DT	ENST00000426529.6	TSL:5	n.27G>A		non_coding_transcript_exon	Exon 1 of 9
	GARS1-DT	ENST00000578994.6	TSL:4	n.93G>A		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4368 AN: 152202 Hom.: 75 Cov.: 33

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.0122

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0239 AC: 10607 AN: 443714 Hom.: 143 Cov.: 4 AF XY: 0.0228 AC XY: 5349 AN XY: 234438

African (AFR) AF: 0.0330 AC: 365 AN: 11060

American (AMR) AF: 0.0203 AC: 373 AN: 18416

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 266 AN: 13334

East Asian (EAS) AF: 0.0000673 AC: 2 AN: 29714

South Asian (SAS) AF: 0.00733 AC: 333 AN: 45448

European-Finnish (FIN) AF: 0.0134 AC: 396 AN: 29532

Middle Eastern (MID) AF: 0.0274 AC: 53 AN: 1936

European-Non Finnish (NFE) AF: 0.0302 AC: 8098 AN: 268554

Other (OTH) AF: 0.0280 AC: 721 AN: 25720

GnomAD4 genome AF: 0.0287 AC: 4378 AN: 152320 Hom.: 77 Cov.: 33 AF XY: 0.0274 AC XY: 2041 AN XY: 74492

African (AFR) AF: 0.0343 AC: 1427 AN: 41568

American (AMR) AF: 0.0278 AC: 426 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4822

European-Finnish (FIN) AF: 0.0122 AC: 130 AN: 10622

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0309 AC: 2101 AN: 68022

Other (OTH) AF: 0.0241 AC: 51 AN: 2114

Alfa AF: 0.0294 Hom.: 13

Bravo AF: 0.0306

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.4
DANN	Benign	0.82
PhyloP100		1.0
PromoterAI		0.013	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: rs17159262; hg19: chr7-30634333;