dbSNP rs777045330: GARS1:c.-85C>A (chr7-30594837-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_001316772.1(GARS1):c.-247C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,209,632 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 16 hom. )

Consequence

GARS1
NM_001316772.1 5_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 1.95

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 links:

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

GARS1-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 7-30594837-C-A is Benign according to our data. Variant chr7-30594837-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 910466.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00225 (342/152308) while in subpopulation NFE AF = 0.000662 (45/68014). AF 95% confidence interval is 0.000508. There are 6 homozygotes in GnomAd4. There are 257 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 342 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316772.1. 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_001316772.1		c.-247C>A		5_prime_UTR	Exon 1 of 17	NP_001303701.1	P41250-2
	GARS1	NM_002047.4	MANE Select	c.-85C>A		upstream_gene	N/A	NP_002038.2	P41250-1

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
GARS1	ENST00000675810.1	c.-85C>A	5_prime_UTR	Exon 1 of 16	ENSP00000502743.1	A0A6Q8PHH9
GARS1	ENST00000675051.1	c.22-3959C>A	intron	N/A	ENSP00000502296.1	A0A6Q8PGI6
GARS1	ENST00000674643.1	n.-85C>A	non_coding_transcript_exon	Exon 1 of 17	ENSP00000501636.1	A0A6Q8PF45

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

342

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0274

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

0.00118

AC:

1246

AN:

1057324

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

556

AN XY:

530862

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23756

American (AMR)

AF:

0.0000358

AC:

AN:

27968

Ashkenazi Jewish (ASJ)

AF:

0.000325

AC:

AN:

21570

East Asian (EAS)

AF:

0.0000602

AC:

AN:

33232

South Asian (SAS)

AF:

0.0000581

AC:

AN:

68856

European-Finnish (FIN)

AF:

0.0290

AC:

956

AN:

32988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3408

European-Non Finnish (NFE)

AF:

0.000250

AC:

200

AN:

799202

Other (OTH)

AF:

0.00164

AC:

AN:

46344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

157

235

314

392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.00225

AC:

342

AN:

152308

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

257

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41572

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0274

AC:

291

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000662

AC:

AN:

68014

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00259

Hom.:

Bravo

AF:

0.000215

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Charcot-Marie-Tooth disease type 2D (1)

Distal spinal muscular atrophy (1)

Neuronopathy, distal hereditary motor, type 5A (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

1.9

PromoterAI

-0.33

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over