NM_004446.3:c.2182-1102C>T

Variant summary

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

The NM_004446.3(EPRS1):​c.2182-1102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,052 control chromosomes in the GnomAD database, including 49,087 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 0.80 ( 49087 hom., cov: 31)

Consequence

EPRS1
NM_004446.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.313

Publications

4 publications found
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]
EPRS1 Gene-Disease associations (from GenCC):
  • leukodystrophy, hypomyelinating, 15
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

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=-1.02).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EPRS1NM_004446.3 linkc.2182-1102C>T intron_variant Intron 17 of 31 ENST00000366923.8 NP_004437.2 P07814

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EPRS1ENST00000366923.8 linkc.2182-1102C>T intron_variant Intron 17 of 31 1 NM_004446.3 ENSP00000355890.3 P07814
EPRS1ENST00000609181.5 linkc.2203-1102C>T intron_variant Intron 18 of 20 1 ENSP00000477245.1 V9GYZ6
EPRS1ENST00000464052.5 linkn.604-1102C>T intron_variant Intron 4 of 4 2

Frequencies

GnomAD3 genomes
AF:
0.802
AC:
121878
AN:
151934
Hom.:
49048
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.761
Gnomad AMI
AF:
0.775
Gnomad AMR
AF:
0.848
Gnomad ASJ
AF:
0.721
Gnomad EAS
AF:
0.929
Gnomad SAS
AF:
0.837
Gnomad FIN
AF:
0.817
Gnomad MID
AF:
0.787
Gnomad NFE
AF:
0.807
Gnomad OTH
AF:
0.796
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.802
AC:
121971
AN:
152052
Hom.:
49087
Cov.:
31
AF XY:
0.804
AC XY:
59739
AN XY:
74310
show subpopulations
African (AFR)
AF:
0.761
AC:
31534
AN:
41438
American (AMR)
AF:
0.848
AC:
12969
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.721
AC:
2501
AN:
3470
East Asian (EAS)
AF:
0.929
AC:
4814
AN:
5182
South Asian (SAS)
AF:
0.835
AC:
4022
AN:
4814
European-Finnish (FIN)
AF:
0.817
AC:
8623
AN:
10550
Middle Eastern (MID)
AF:
0.774
AC:
226
AN:
292
European-Non Finnish (NFE)
AF:
0.807
AC:
54893
AN:
67996
Other (OTH)
AF:
0.797
AC:
1682
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1221
2443
3664
4886
6107
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
878
1756
2634
3512
4390
<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:
0.806
Hom.:
6713
Bravo
AF:
0.801
Asia WGS
AF:
0.889
AC:
3089
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.35
DANN
Benign
0.48
PhyloP100
-0.31
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2647430; hg19: chr1-220171786; API