rs2577138

Variant names:

• chr1-220032638-A-C
• rs2577138
• NM_004446.3:c.389-112T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-220032638-A-C
• chr1-220032638-A-G
• chr1-220032638-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004446.3(EPRS1):​c.389-112T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,013,494 control chromosomes in the GnomAD database, including 335,458 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 (49088 hom., cov: 33)
  • Exomes 𝑓: 0.81 (286370 hom.)
• Consequence: EPRS1 NM_004446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.726
• Publications: 5 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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
EPRS1	NM_004446.3	c.389-112T>G		intron_variant	Intron 4 of 31	ENST00000366923.8	NP_004437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPRS1	ENST00000366923.8	c.389-112T>G		intron_variant	Intron 4 of 31	1	NM_004446.3	ENSP00000355890.3
EPRS1	ENST00000609181.5	c.389-112T>G		intron_variant	Intron 4 of 20	1		ENSP00000477245.1
EPRS1	ENST00000477030.2	n.389-112T>G		intron_variant	Intron 4 of 11	1		ENSP00000477493.1

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121920 AN: 152038 Hom.: 49049 Cov.: 33

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.796

GnomAD4 exome AF: 0.814 AC: 701232 AN: 861338 Hom.: 286370 AF XY: 0.814 AC XY: 366987 AN XY: 450980

African (AFR) AF: 0.762 AC: 15149 AN: 19870

American (AMR) AF: 0.890 AC: 28625 AN: 32150

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 15630 AN: 21458

East Asian (EAS) AF: 0.924 AC: 33500 AN: 36266

South Asian (SAS) AF: 0.828 AC: 56122 AN: 67758

European-Finnish (FIN) AF: 0.823 AC: 33188 AN: 40330

Middle Eastern (MID) AF: 0.772 AC: 3274 AN: 4242

European-Non Finnish (NFE) AF: 0.807 AC: 483141 AN: 598818

Other (OTH) AF: 0.806 AC: 32603 AN: 40446

GnomAD4 genome AF: 0.802 AC: 122013 AN: 152156 Hom.: 49088 Cov.: 33 AF XY: 0.804 AC XY: 59783 AN XY: 74400

African (AFR) AF: 0.760 AC: 31550 AN: 41486

American (AMR) AF: 0.848 AC: 12965 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2500 AN: 3468

East Asian (EAS) AF: 0.929 AC: 4807 AN: 5174

South Asian (SAS) AF: 0.836 AC: 4035 AN: 4824

European-Finnish (FIN) AF: 0.816 AC: 8645 AN: 10598

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54895 AN: 68008

Other (OTH) AF: 0.797 AC: 1683 AN: 2112

Alfa AF: 0.808 Hom.: 9476

Bravo AF: 0.801

Asia WGS AF: 0.889 AC: 3092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.32
PhyloP100		0.73
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

Other links and lift over

dbSNP: rs2577138; hg19: chr1-220205980;