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GeneBe

rs5030754

chr1-219983387-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_004446.3(EPRS1):c.3102G>A(p.Lys1034=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 1,605,802 control chromosomes in the GnomAD database, including 7,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1366 hom., cov: 33)
Exomes 𝑓: 0.087 ( 6328 hom. )

Consequence

EPRS1
NM_004446.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05
Variant links:
Genes affected
EPRS1 (HGNC:3418): (glutamyl-prolyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a multifunctional aminoacyl-tRNA synthetase that catalyzes the aminoacylation of glutamic acid and proline tRNA species. Alternative splicing has been observed for this gene, but the full-length nature and biological validity of the variant have not been determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-219983387-C-T is Benign according to our data. Variant chr1-219983387-C-T is described in ClinVar as [Benign]. Clinvar id is 1166607.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.05 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EPRS1NM_004446.3 linkuse as main transcriptc.3102G>A p.Lys1034= synonymous_variant 22/32 ENST00000366923.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPRS1ENST00000366923.8 linkuse as main transcriptc.3102G>A p.Lys1034= synonymous_variant 22/321 NM_004446.3 P1
EPRS1ENST00000485821.1 linkuse as main transcriptn.65G>A non_coding_transcript_exon_variant 2/33

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.119
AC:
18031
AN:
152130
Hom.:
1365
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.217
Gnomad AMI
AF:
0.0888
Gnomad AMR
AF:
0.0767
Gnomad ASJ
AF:
0.0334
Gnomad EAS
AF:
0.0625
Gnomad SAS
AF:
0.0410
Gnomad FIN
AF:
0.0619
Gnomad MID
AF:
0.0728
Gnomad NFE
AF:
0.0922
Gnomad OTH
AF:
0.103
GnomAD3 exomes
AF:
0.0798
AC:
19772
AN:
247864
Hom.:
1014
AF XY:
0.0765
AC XY:
10240
AN XY:
133838
show subpopulations
Gnomad AFR exome
AF:
0.219
Gnomad AMR exome
AF:
0.0493
Gnomad ASJ exome
AF:
0.0315
Gnomad EAS exome
AF:
0.0637
Gnomad SAS exome
AF:
0.0336
Gnomad FIN exome
AF:
0.0675
Gnomad NFE exome
AF:
0.0903
Gnomad OTH exome
AF:
0.0816
GnomAD4 exome
AF:
0.0870
AC:
126456
AN:
1453554
Hom.:
6328
Cov.:
31
AF XY:
0.0849
AC XY:
61384
AN XY:
723168
show subpopulations
Gnomad4 AFR exome
AF:
0.229
Gnomad4 AMR exome
AF:
0.0542
Gnomad4 ASJ exome
AF:
0.0324
Gnomad4 EAS exome
AF:
0.0602
Gnomad4 SAS exome
AF:
0.0349
Gnomad4 FIN exome
AF:
0.0721
Gnomad4 NFE exome
AF:
0.0911
Gnomad4 OTH exome
AF:
0.0886
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.119
AC:
18066
AN:
152248
Hom.:
1366
Cov.:
33
AF XY:
0.113
AC XY:
8415
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.217
Gnomad4 AMR
AF:
0.0766
Gnomad4 ASJ
AF:
0.0334
Gnomad4 EAS
AF:
0.0628
Gnomad4 SAS
AF:
0.0414
Gnomad4 FIN
AF:
0.0619
Gnomad4 NFE
AF:
0.0922
Gnomad4 OTH
AF:
0.102
Alfa
AF:
0.102
Hom.:
465
Bravo
AF:
0.125
Asia WGS
AF:
0.0580
AC:
202
AN:
3478
EpiCase
AF:
0.0916
EpiControl
AF:
0.0867

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 30, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.24
Cadd
Benign
6.7
Dann
Benign
0.76

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.

Other links and lift over

dbSNP: rs5030754; hg19: chr1-220156729; COSMIC: COSV65099293; COSMIC: COSV65099293; API