rs2789809

Variant names:

• chr1-220011706-C-G
• rs2789809
• NM_004446.3:c.1495-650G>C

Variant summary

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

The NM_004446.3(EPRS1):​c.1495-650G>C 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 152,146 control chromosomes in the GnomAD database, including 49,100 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 (49100 hom., cov: 32)
• Consequence: EPRS1 NM_004446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 3 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=-0.89).
• 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.1495-650G>C		intron_variant	Intron 12 of 31	ENST00000366923.8	NP_004437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPRS1	ENST00000366923.8	c.1495-650G>C		intron_variant	Intron 12 of 31	1	NM_004446.3	ENSP00000355890.3
EPRS1	ENST00000609181.5	c.1516-650G>C		intron_variant	Intron 13 of 20	1		ENSP00000477245.1
EPRS1	ENST00000477030.2	n.*521-650G>C		intron_variant	Intron 9 of 11	1		ENSP00000477493.1

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121935 AN: 152028 Hom.: 49061 Cov.: 32

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: 0.838

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.795

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.802 AC: 122028 AN: 152146 Hom.: 49100 Cov.: 32 AF XY: 0.804 AC XY: 59784 AN XY: 74378

African (AFR) AF: 0.761 AC: 31570 AN: 41490

American (AMR) AF: 0.848 AC: 12979 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2502 AN: 3470

East Asian (EAS) AF: 0.929 AC: 4808 AN: 5174

South Asian (SAS) AF: 0.836 AC: 4035 AN: 4826

European-Finnish (FIN) AF: 0.817 AC: 8642 AN: 10578

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

European-Non Finnish (NFE) AF: 0.807 AC: 54874 AN: 67988

Other (OTH) AF: 0.796 AC: 1684 AN: 2116

Alfa AF: 0.805 Hom.: 6121

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	-0.89
CADD	Benign	0.91
DANN	Benign	0.46
PhyloP100		-0.29
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: rs2789809; hg19: chr1-220185048;