rs374795892

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002047.4(GARS1):c.1613+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

GARS1
NM_002047.4 splice_region, intron

Scores

Splicing: ADA: 0.0004422

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.138

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease type 2D
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
neuronopathy, distal hereditary motor, type 5A
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, Laboratory for Molecular Medicine
spinal muscular atrophy, infantile, James type
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

GARS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 7-30622469-T-C is Benign according to our data. Variant chr7-30622469-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 476752.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4 link	c.1613+7T>C		splice_region_variant, intron_variant	Intron 12 of 16	ENST00000389266.8	NP_002038.2	P41250-1
GARS1	NM_001316772.1 link	c.1451+7T>C		splice_region_variant, intron_variant	Intron 12 of 16		NP_001303701.1	P41250-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GARS1	ENST00000389266.8 link	c.1613+7T>C	splice_region_variant, intron_variant	Intron 12 of 16	1	NM_002047.4	ENSP00000373918.3	P41250-1
GARS1	ENST00000675651.1 link	c.1613+7T>C	splice_region_variant, intron_variant	Intron 12 of 16			ENSP00000502513.1	A0A6Q8PGZ8
GARS1	ENST00000675810.1 link	c.1511+7T>C	splice_region_variant, intron_variant	Intron 11 of 15			ENSP00000502743.1	A0A6Q8PHH9
GARS1	ENST00000675693.1 link	c.1445+7T>C	splice_region_variant, intron_variant	Intron 13 of 17			ENSP00000502174.1	A0A6Q8PGA8
GARS1	ENST00000675051.1 link	c.1412+7T>C	splice_region_variant, intron_variant	Intron 12 of 16			ENSP00000502296.1	A0A6Q8PGI6
GARS1	ENST00000674815.1 link	c.1244+7T>C	splice_region_variant, intron_variant	Intron 12 of 16			ENSP00000502799.1	A0A6Q8PGW4
GARS1	ENST00000674851.1 link	c.1244+7T>C	splice_region_variant, intron_variant	Intron 13 of 17			ENSP00000502451.1	A0A6Q8PGW4
GARS1	ENST00000444666.6 link	n.1613+7T>C	splice_region_variant, intron_variant	Intron 12 of 17	3		ENSP00000415447.2	H7C443
GARS1	ENST00000674616.1 link	n.*1327+7T>C	splice_region_variant, intron_variant	Intron 13 of 17			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 link	n.*713+7T>C	splice_region_variant, intron_variant	Intron 13 of 16			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 link	n.*951+7T>C	splice_region_variant, intron_variant	Intron 13 of 17			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 link	n.1613+7T>C	splice_region_variant, intron_variant	Intron 12 of 15			ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 link	n.*1483+7T>C	splice_region_variant, intron_variant	Intron 13 of 17			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 link	n.1613+7T>C	splice_region_variant, intron_variant	Intron 12 of 14			ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 link	n.*1555+7T>C	splice_region_variant, intron_variant	Intron 14 of 18			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 link	n.*558+7T>C	splice_region_variant, intron_variant	Intron 12 of 16			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676164.1 link	n.*1064+7T>C	splice_region_variant, intron_variant	Intron 12 of 16			ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 link	n.*902+7T>C	splice_region_variant, intron_variant	Intron 13 of 17			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 link	n.*1045+7T>C	splice_region_variant, intron_variant	Intron 12 of 16			ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 link	n.1613+7T>C	splice_region_variant, intron_variant	Intron 12 of 15			ENSP00000502681.1	A0A6Q8PHI7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

249504

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1111934

Other (OTH)

AF:

0.0000166

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease type 2

Benign:1

Oct 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.4

(source)

DANN

Benign

0.71

PhyloP100

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00044

dbscSNV1_RF

Benign

0.016

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over