dbSNP rs5030754: EPRS1:p.Lys1034Lys (chr1-219983387-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004446.3(EPRS1):c.3102G>A(p.Lys1034Lys) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.05

Publications

11 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

EPRS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

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

BP6

Variant 1-219983387-C-T is Benign according to our data. Variant chr1-219983387-C-T is described in ClinVar as Benign. ClinVar VariationId is 1166607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.05 with no splicing effect.

BA1

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 rank	MANE	Protein	UniProt
EPRS1	NM_004446.3 link	c.3102G>A	p.Lys1034Lys	synonymous_variant	Exon 22 of 32	ENST00000366923.8	NP_004437.2	P07814

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPRS1	ENST00000366923.8 link	c.3102G>A	p.Lys1034Lys	synonymous_variant	Exon 22 of 32	1	NM_004446.3	ENSP00000355890.3		P07814
EPRS1	ENST00000485821.1 link	n.65G>A		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18031

AN:

152130

Hom.:

1365

Cov.:

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

GnomAD2 exomes

AF:

0.0798

AC:

19772

AN:

247864

AF XY:

0.0765

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 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.:

AF XY:

0.0849

AC XY:

61384

AN XY:

723168

show subpopulations

African (AFR)

AF:

0.229

AC:

7587

AN:

33156

American (AMR)

AF:

0.0542

AC:

2400

AN:

44270

Ashkenazi Jewish (ASJ)

AF:

0.0324

AC:

843

AN:

26020

East Asian (EAS)

AF:

0.0602

AC:

2385

AN:

39616

South Asian (SAS)

AF:

0.0349

AC:

2974

AN:

85334

European-Finnish (FIN)

AF:

0.0721

AC:

3847

AN:

53382

Middle Eastern (MID)

AF:

0.0683

AC:

392

AN:

5740

European-Non Finnish (NFE)

AF:

0.0911

AC:

100702

AN:

1105902

Other (OTH)

AF:

0.0886

AC:

5326

AN:

60134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

4826

9651

14477

19302

24128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3680

7360

11040

14720

18400

<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:

0.119

AC:

18066

AN:

152248

Hom.:

1366

Cov.:

AF XY:

0.113

AC XY:

8415

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.217

AC:

9008

AN:

41516

American (AMR)

AF:

0.0766

AC:

1172

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0334

AC:

116

AN:

3470

East Asian (EAS)

AF:

0.0628

AC:

325

AN:

5176

South Asian (SAS)

AF:

0.0414

AC:

200

AN:

4828

European-Finnish (FIN)

AF:

0.0619

AC:

657

AN:

10620

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0922

AC:

6269

AN:

68022

Other (OTH)

AF:

0.102

AC:

216

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

810

1620

2429

3239

4049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<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:

0.102

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

6.7

(source)

DANN

Benign

0.76

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over