dbSNP rs2305737: RARS1:c.*66C>A (chr5-168519256-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002887.4(RARS1):c.*66C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,253,058 control chromosomes in the GnomAD database, including 2,446 homozygotes. 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 0.043 ( 444 hom., cov: 32)

Exomes 𝑓: 0.027 ( 2002 hom. )

Consequence

RARS1
NM_002887.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.470

Publications

5 publications found

Variant links:

Genes affected

RARS1 (HGNC:9870): (arginyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Arginyl-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family. [provided by RefSeq, Jul 2008]

RARS1 Gene-Disease associations (from GenCC):

hypomyelinating leukodystrophy 9
Inheritance: AR, Unknown Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, G2P

RARS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARS1	NM_002887.4 link	c.*66C>A		3_prime_UTR_variant	Exon 15 of 15	ENST00000231572.8	NP_002878.2	P54136-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RARS1	ENST00000231572.8 link	c.*66C>A	3_prime_UTR_variant	Exon 15 of 15	1	NM_002887.4	ENSP00000231572.3	P54136-1
RARS1	ENST00000520013.5 link	n.*1550C>A	non_coding_transcript_exon_variant	Exon 14 of 14	2		ENSP00000429030.1	E5RJM9
RARS1	ENST00000520013.5 link	n.*1550C>A	3_prime_UTR_variant	Exon 14 of 14	2		ENSP00000429030.1	E5RJM9

Frequencies

GnomAD3 genomes

AF:

0.0430

AC:

6536

AN:

152080

Hom.:

442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0370

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.0431

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.0415

GnomAD4 exome

AF:

0.0272

AC:

29891

AN:

1100858

Hom.:

2002

Cov.:

AF XY:

0.0258

AC XY:

14392

AN XY:

557344

show subpopulations

African (AFR)

AF:

0.0379

AC:

968

AN:

25520

American (AMR)

AF:

0.267

AC:

9651

AN:

36100

Ashkenazi Jewish (ASJ)

AF:

0.0111

AC:

259

AN:

23326

East Asian (EAS)

AF:

0.137

AC:

4986

AN:

36432

South Asian (SAS)

AF:

0.0337

AC:

2433

AN:

72222

European-Finnish (FIN)

AF:

0.0433

AC:

2269

AN:

52370

Middle Eastern (MID)

AF:

0.0129

AC:

AN:

4958

European-Non Finnish (NFE)

AF:

0.00974

AC:

7810

AN:

801806

Other (OTH)

AF:

0.0302

AC:

1451

AN:

48124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1223

2445

3668

4890

6113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.0431

AC:

6553

AN:

152200

Hom.:

444

Cov.:

AF XY:

0.0479

AC XY:

3566

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0372

AC:

1545

AN:

41530

American (AMR)

AF:

0.183

AC:

2804

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3468

East Asian (EAS)

AF:

0.125

AC:

646

AN:

5182

South Asian (SAS)

AF:

0.0357

AC:

172

AN:

4824

European-Finnish (FIN)

AF:

0.0431

AC:

457

AN:

10598

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0115

AC:

785

AN:

67990

Other (OTH)

AF:

0.0406

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

293

586

880

1173

1466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0208

Hom.:

199

Bravo

AF:

0.0557

Asia WGS

AF:

0.0900

AC:

313

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over