chr7-30622471-T-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002047.4(GARS1):c.1613+9T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GARS1
NM_002047.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0470

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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 7-30622471-T-A is Benign according to our data. Variant chr7-30622471-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1160502.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4 link	c.1613+9T>A		intron_variant	Intron 12 of 16	ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1 link	c.1451+9T>A		intron_variant	Intron 12 of 16		NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
GARS1	ENST00000389266.8 link	c.1613+9T>A	intron_variant	Intron 12 of 16	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1 link	c.1613+9T>A	intron_variant	Intron 12 of 16			ENSP00000502513.1
GARS1	ENST00000675810.1 link	c.1511+9T>A	intron_variant	Intron 11 of 15			ENSP00000502743.1
GARS1	ENST00000675693.1 link	c.1445+9T>A	intron_variant	Intron 13 of 17			ENSP00000502174.1
GARS1	ENST00000675051.1 link	c.1412+9T>A	intron_variant	Intron 12 of 16			ENSP00000502296.1
GARS1	ENST00000674815.1 link	c.1244+9T>A	intron_variant	Intron 12 of 16			ENSP00000502799.1
GARS1	ENST00000674851.1 link	c.1244+9T>A	intron_variant	Intron 13 of 17			ENSP00000502451.1
GARS1	ENST00000444666.6 link	n.1613+9T>A	intron_variant	Intron 12 of 17	3		ENSP00000415447.2
GARS1	ENST00000674616.1 link	n.*1327+9T>A	intron_variant	Intron 13 of 17			ENSP00000502408.1
GARS1	ENST00000674643.1 link	n.*713+9T>A	intron_variant	Intron 13 of 16			ENSP00000501636.1
GARS1	ENST00000674737.1 link	n.*951+9T>A	intron_variant	Intron 13 of 17			ENSP00000502464.1
GARS1	ENST00000674807.1 link	n.1613+9T>A	intron_variant	Intron 12 of 15			ENSP00000502814.1
GARS1	ENST00000675529.1 link	n.*1483+9T>A	intron_variant	Intron 13 of 17			ENSP00000501655.1
GARS1	ENST00000675859.1 link	n.1613+9T>A	intron_variant	Intron 12 of 14			ENSP00000502033.1
GARS1	ENST00000676088.1 link	n.*1555+9T>A	intron_variant	Intron 14 of 18			ENSP00000501884.1
GARS1	ENST00000676140.1 link	n.*558+9T>A	intron_variant	Intron 12 of 16			ENSP00000502571.1
GARS1	ENST00000676164.1 link	n.*1064+9T>A	intron_variant	Intron 12 of 16			ENSP00000501986.1
GARS1	ENST00000676210.1 link	n.*902+9T>A	intron_variant	Intron 13 of 17			ENSP00000502373.1
GARS1	ENST00000676259.1 link	n.*1045+9T>A	intron_variant	Intron 12 of 16			ENSP00000501980.1
GARS1	ENST00000676403.1 link	n.1613+9T>A	intron_variant	Intron 12 of 15			ENSP00000502681.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727176

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111900

Other (OTH)

AF:

0.00

AC:

AN:

60376

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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.:

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

Feb 03, 2020

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

-0.74

CADD

Benign

1.9

(source)

DANN

Benign

0.77

PhyloP100

-0.047

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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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