chr5-168486505-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002887.4(RARS1):c.7G>A(p.Val3Ile) variant causes a missense change. The variant allele was found at a frequency of 0.573 in 1,558,010 control chromosomes in the GnomAD database, including 260,198 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V3L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.63 ( 30732 hom., cov: 32)

Exomes 𝑓: 0.57 ( 229466 hom. )

Consequence

RARS1
NM_002887.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.08

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.688819E-7).

BP6

Variant 5-168486505-G-A is Benign according to our data. Variant chr5-168486505-G-A is described in ClinVar as [Benign]. Clinvar id is 380030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARS1	NM_002887.4 link	c.7G>A	p.Val3Ile	missense_variant	Exon 1 of 15	ENST00000231572.8	NP_002878.2	P54136-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARS1	ENST00000231572.8 link	c.7G>A	p.Val3Ile	missense_variant	Exon 1 of 15	1	NM_002887.4	ENSP00000231572.3		P54136-1

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95388

AN:

151908

Hom.:

30686

Cov.:

show subpopulations

Gnomad AFR

AF:

0.739

Gnomad AMI

AF:

0.539

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.877

Gnomad SAS

AF:

0.513

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.605

GnomAD2 exomes

AF:

0.602

AC:

100196

AN:

166308

AF XY:

0.588

show subpopulations

Gnomad AFR exome

AF:

0.737

Gnomad AMR exome

AF:

0.736

Gnomad ASJ exome

AF:

0.478

Gnomad EAS exome

AF:

0.874

Gnomad FIN exome

AF:

0.566

Gnomad NFE exome

AF:

0.542

Gnomad OTH exome

AF:

0.579

GnomAD4 exome

AF:

0.567

AC:

796618

AN:

1405984

Hom.:

229466

Cov.:

AF XY:

0.563

AC XY:

390909

AN XY:

694020

show subpopulations

Gnomad4 AFR exome

AF:

0.740

AC:

24012

AN:

32456

Gnomad4 AMR exome

AF:

0.728

AC:

26114

AN:

35868

Gnomad4 ASJ exome

AF:

0.486

AC:

12253

AN:

25192

Gnomad4 EAS exome

AF:

0.880

AC:

32558

AN:

36986

Gnomad4 SAS exome

AF:

0.506

AC:

40414

AN:

79818

Gnomad4 FIN exome

AF:

0.567

AC:

28087

AN:

49558

Gnomad4 NFE exome

AF:

0.550

AC:

595535

AN:

1082064

Gnomad4 Remaining exome

AF:

0.589

AC:

34354

AN:

58348

Heterozygous variant carriers

16930

33859

50789

67718

84648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

17066

34132

51198

68264

85330

<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:

0.628

AC:

95487

AN:

152026

Hom.:

30732

Cov.:

AF XY:

0.631

AC XY:

46900

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.739

AC:

0.739088

AN:

0.739088

Gnomad4 AMR

AF:

0.687

AC:

0.687008

AN:

0.687008

Gnomad4 ASJ

AF:

0.497

AC:

0.497115

AN:

0.497115

Gnomad4 EAS

AF:

0.877

AC:

0.876986

AN:

0.876986

Gnomad4 SAS

AF:

0.512

AC:

0.512251

AN:

0.512251

Gnomad4 FIN

AF:

0.569

AC:

0.569119

AN:

0.569119

Gnomad4 NFE

AF:

0.554

AC:

0.554285

AN:

0.554285

Gnomad4 OTH

AF:

0.609

AC:

0.608634

AN:

0.608634

Heterozygous variant carriers

1773

3546

5319

7092

8865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.576

Hom.:

111917

Bravo

AF:

0.650

TwinsUK

AF:

0.546

AC:

2026

ALSPAC

AF:

0.561

AC:

2163

ESP6500AA

AF:

0.753

AC:

3246

ESP6500EA

AF:

0.553

AC:

4685

ExAC

AF:

0.503

AC:

49127

Asia WGS

AF:

0.696

AC:

2418

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypomyelinating leukodystrophy 9

Benign:2

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 02, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.43

T;T

MetaRNN

Benign

9.7e-7

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.10

N;.

REVEL

Benign

0.10

Sift

Benign

0.19

T;.

Sift4G

Benign

0.21

T;T

Polyphen

0.0010

B;.

Vest4

0.13

MPC

0.10

ClinPred

0.042

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.095

Mutation Taster

=297/3

polymorphism (auto)

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over