rs2072236

Variant names:

• chr7-30595148-C-T
• rs2072236
• NM_002047.4:c.222+5C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-30595148-C-T
• chr7-30595148-C-A
• chr7-30595148-C-G

Variant summary

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

The NM_002047.4(GARS1):​c.222+5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0984 in 1,535,676 control chromosomes in the GnomAD database, including 8,528 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (882 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7646 hom.)
• Consequence: GARS1 NM_002047.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001381
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.00800
• Publications: 17 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=-0.51).
• BP6: Variant 7-30595148-C-T is Benign according to our data. Variant chr7-30595148-C-T is described in ClinVar as Benign. ClinVar VariationId is 137439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARS1	NM_002047.4	MANE Select	c.222+5C>T		splice_region intron	N/A	NP_002038.2	P41250-1
	GARS1	NM_001316772.1		c.60+5C>T		splice_region intron	N/A	NP_001303701.1	P41250-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARS1	ENST00000389266.8	TSL:1 MANE Select	c.222+5C>T		splice_region intron	N/A	ENSP00000373918.3	P41250-1
	GARS1	ENST00000675651.1		c.222+5C>T		splice_region intron	N/A	ENSP00000502513.1	A0A6Q8PGZ8
	GARS1	ENST00000675810.1		c.222+5C>T		splice_region intron	N/A	ENSP00000502743.1	A0A6Q8PHH9

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15547 AN: 152122 Hom.: 880 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0932

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0614

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.128

GnomAD2 exomes AF: 0.113 AC: 15584 AN: 138328 AF XY: 0.117

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.0757

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.160

Gnomad FIN exome AF: 0.0619

Gnomad NFE exome AF: 0.0923

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.0980 AC: 135578 AN: 1383436 Hom.: 7646 Cov.: 35 AF XY: 0.100 AC XY: 68563 AN XY: 682804

African (AFR) AF: 0.120 AC: 3776 AN: 31582

American (AMR) AF: 0.0785 AC: 2804 AN: 35714

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2812 AN: 25166

East Asian (EAS) AF: 0.194 AC: 6937 AN: 35770

South Asian (SAS) AF: 0.187 AC: 14797 AN: 79184

European-Finnish (FIN) AF: 0.0628 AC: 2183 AN: 34750

Middle Eastern (MID) AF: 0.149 AC: 837 AN: 5606

European-Non Finnish (NFE) AF: 0.0882 AC: 95053 AN: 1077810

Other (OTH) AF: 0.110 AC: 6379 AN: 57854

GnomAD4 genome AF: 0.102 AC: 15558 AN: 152240 Hom.: 882 Cov.: 32 AF XY: 0.103 AC XY: 7671 AN XY: 74442

African (AFR) AF: 0.120 AC: 4974 AN: 41554

American (AMR) AF: 0.0931 AC: 1425 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3472

East Asian (EAS) AF: 0.178 AC: 917 AN: 5156

South Asian (SAS) AF: 0.198 AC: 955 AN: 4818

European-Finnish (FIN) AF: 0.0614 AC: 652 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0876 AC: 5960 AN: 68004

Other (OTH) AF: 0.132 AC: 279 AN: 2114

Alfa AF: 0.0913 Hom.: 966

Bravo AF: 0.106

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

ClinVar submissions

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	-0.51
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		0.0080
PromoterAI		0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.0040
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: rs2072236; hg19: chr7-30634764; COSMIC: COSV66827729; COSMIC: COSV66827729;