rs2647430

Variant names:

• chr1-219998444-G-A
• rs2647430
• NM_004446.3:c.2182-1102C>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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• Publications: 4 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: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004446.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPRS1	NM_004446.3	MANE Select	c.2182-1102C>T		intron	N/A	NP_004437.2	P07814

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPRS1	ENST00000366923.8	TSL:1 MANE Select	c.2182-1102C>T		intron	N/A	ENSP00000355890.3	P07814
	EPRS1	ENST00000609181.5	TSL:1	c.2203-1102C>T		intron	N/A	ENSP00000477245.1	V9GYZ6
	EPRS1	ENST00000927912.1		c.2302-1102C>T		intron	N/A	ENSP00000597971.1

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121878 AN: 151934 Hom.: 49048 Cov.: 31

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

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

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 v4.9

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

Other links and lift over

dbSNP: rs2647430; hg19: chr1-220171786;