chr7-30594858-C-G

Variant names:

• chr7-30594858-C-G
• rs932663016
• ENST00000675810:c.-64C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001316772.1(GARS1):​c.-226C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,387,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: GARS1 NM_001316772.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000526 (8/152166) while in subpopulation AFR AF= 0.000121 (5/41440). AF 95% confidence interval is 0.0000474. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_001316772.1	c.-226C>G		5_prime_UTR_variant	Exon 1 of 17		NP_001303701.1
GARS1	NM_002047.4	c.-64C>G		upstream_gene_variant		ENST00000389266.8	NP_002038.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000675810	c.-64C>G		5_prime_UTR_variant	Exon 1 of 16			ENSP00000502743.1
GARS1	ENST00000674815	c.-242C>G		5_prime_UTR_variant	Exon 1 of 17			ENSP00000502799.1
GARS1	ENST00000675051.1	c.22-3938C>G		intron_variant	Intron 1 of 16			ENSP00000502296.1
GARS1	ENST00000674643.1	n.-64C>G		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000501636.1
GARS1	ENST00000674807.1	n.-64C>G		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.-64C>G		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000501655.1
GARS1	ENST00000676088.1	n.-64C>G		non_coding_transcript_exon_variant	Exon 1 of 19			ENSP00000501884.1
GARS1	ENST00000676210.1	n.-64C>G		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502373.1
GARS1	ENST00000676403.1	n.-64C>G		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000502681.1
GARS1	ENST00000674643.1	n.-64C>G		5_prime_UTR_variant	Exon 1 of 17			ENSP00000501636.1
GARS1	ENST00000674807.1	n.-64C>G		5_prime_UTR_variant	Exon 1 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.-64C>G		5_prime_UTR_variant	Exon 1 of 18			ENSP00000501655.1
GARS1	ENST00000676088.1	n.-64C>G		5_prime_UTR_variant	Exon 1 of 19			ENSP00000501884.1
GARS1	ENST00000676210.1	n.-64C>G		5_prime_UTR_variant	Exon 1 of 18			ENSP00000502373.1
GARS1	ENST00000676403.1	n.-64C>G		5_prime_UTR_variant	Exon 1 of 16			ENSP00000502681.1
GARS1	ENST00000389266.8	c.-64C>G		upstream_gene_variant		1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.-64C>G		upstream_gene_variant				ENSP00000502513.1
GARS1	ENST00000675693.1	c.-64C>G		upstream_gene_variant				ENSP00000502174.1
GARS1	ENST00000674851.1	c.-278C>G		upstream_gene_variant				ENSP00000502451.1
GARS1	ENST00000444666.6	n.-64C>G		upstream_gene_variant		3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.-64C>G		upstream_gene_variant				ENSP00000502408.1
GARS1	ENST00000674737.1	n.-64C>G		upstream_gene_variant				ENSP00000502464.1
GARS1	ENST00000675859.1	n.-64C>G		upstream_gene_variant				ENSP00000502033.1
GARS1	ENST00000676140.1	n.-64C>G		upstream_gene_variant				ENSP00000502571.1
GARS1	ENST00000676164.1	n.-64C>G		upstream_gene_variant				ENSP00000501986.1
GARS1	ENST00000676259.1	n.-64C>G		upstream_gene_variant				ENSP00000501980.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152166 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000227 AC: 28 AN: 1234894 Hom.: 0 Cov.: 18 AF XY: 0.0000227 AC XY: 14 AN XY: 616026

Gnomad4 AFR exome AF: 0.000178

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000232

Gnomad4 OTH exome AF: 0.0000190

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152166 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74342

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000694 Hom.: 0

Bravo AF: 0.0000529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.8
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs932663016; hg19: chr7-30634474; COSMIC: COSV66828404; COSMIC: COSV66828404;