Genetic Variant NM_002047.4:c.-40C>T (chr7-30594882-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_002047.4(GARS1):c.-40C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0000227 in 1,495,656 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 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

GARS1
NM_002047.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.97

Variant links:

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 links:

GARS1-DT (HGNC:48951): (GARS1 divergent transcript)

GARS1-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000046 (7/152162) while in subpopulation AMR AF= 0.000393 (6/15286). AF 95% confidence interval is 0.00017. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4 link	c.-40C>T		5_prime_UTR_variant	Exon 1 of 17	ENST00000389266.8	NP_002038.2	P41250-1
GARS1	NM_001316772.1 link	c.-202C>T		5_prime_UTR_variant	Exon 1 of 17		NP_001303701.1	P41250-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GARS1	ENST00000389266 link	c.-40C>T	5_prime_UTR_variant	Exon 1 of 17	1	NM_002047.4	ENSP00000373918.3	P41250-1
GARS1	ENST00000675651 link	c.-40C>T	5_prime_UTR_variant	Exon 1 of 17			ENSP00000502513.1	A0A6Q8PGZ8
GARS1	ENST00000675810 link	c.-40C>T	5_prime_UTR_variant	Exon 1 of 16			ENSP00000502743.1	A0A6Q8PHH9
GARS1	ENST00000675693 link	c.-40C>T	5_prime_UTR_variant	Exon 1 of 18			ENSP00000502174.1	A0A6Q8PGA8
GARS1	ENST00000674815 link	c.-218C>T	5_prime_UTR_variant	Exon 1 of 17			ENSP00000502799.1	A0A6Q8PGW4
GARS1	ENST00000675051.1 link	c.22-3914C>T	intron_variant	Intron 1 of 16			ENSP00000502296.1	A0A6Q8PGI6
GARS1	ENST00000674616.1 link	n.-40C>T	non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 link	n.-40C>T	non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 link	n.-40C>T	non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 link	n.-40C>T	non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 link	n.-40C>T	non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 link	n.-40C>T	non_coding_transcript_exon_variant	Exon 1 of 15			ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 link	n.-40C>T	non_coding_transcript_exon_variant	Exon 1 of 19			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 link	n.-40C>T	non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676210.1 link	n.-40C>T	non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 link	n.-40C>T	non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 link	n.-40C>T	non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000502681.1	A0A6Q8PHI7
GARS1	ENST00000674616.1 link	n.-40C>T	5_prime_UTR_variant	Exon 1 of 18			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 link	n.-40C>T	5_prime_UTR_variant	Exon 1 of 17			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 link	n.-40C>T	5_prime_UTR_variant	Exon 1 of 18			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 link	n.-40C>T	5_prime_UTR_variant	Exon 1 of 16			ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 link	n.-40C>T	5_prime_UTR_variant	Exon 1 of 18			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 link	n.-40C>T	5_prime_UTR_variant	Exon 1 of 15			ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 link	n.-40C>T	5_prime_UTR_variant	Exon 1 of 19			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 link	n.-40C>T	5_prime_UTR_variant	Exon 1 of 17			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676210.1 link	n.-40C>T	5_prime_UTR_variant	Exon 1 of 18			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 link	n.-40C>T	5_prime_UTR_variant	Exon 1 of 17			ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 link	n.-40C>T	5_prime_UTR_variant	Exon 1 of 16			ENSP00000502681.1	A0A6Q8PHI7
GARS1	ENST00000674851.1 link	c.-254C>T	upstream_gene_variant				ENSP00000502451.1	A0A6Q8PGW4
GARS1	ENST00000444666.6 link	n.-40C>T	upstream_gene_variant		3		ENSP00000415447.2	H7C443
GARS1	ENST00000676164.1 link	n.-40C>T	upstream_gene_variant				ENSP00000501986.1	A0A6Q8PFV5

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000391

AC:

AN:

127826

Hom.:

AF XY:

0.0000143

AC XY:

AN XY:

70114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000210

Gnomad OTH exome

AF:

0.000257

GnomAD4 exome

AF:

0.0000201

AC:

AN:

1343494

Hom.:

Cov.:

AF XY:

0.0000120

AC XY:

AN XY:

664742

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000198

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:

0.0000134

Gnomad4 OTH exome

AF:

0.000107

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000869

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over