rs2577138

chr1-220032638-A-Cchr1-220032638-A-Gchr1-220032638-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EPRS1	NM_004446.3	c.389-112T>G		intron_variant		ENST00000366923.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPRS1	ENST00000366923.8	c.389-112T>G		intron_variant		1	NM_004446.3	P1
EPRS1	ENST00000609181.5	c.389-112T>G		intron_variant		1
EPRS1	ENST00000477030.2	c.389-112T>G		intron_variant, NMD_transcript_variant		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

Gnomad4 AFR exome AF: 0.762

Gnomad4 AMR exome AF: 0.890

Gnomad4 ASJ exome AF: 0.728

Gnomad4 EAS exome AF: 0.924

Gnomad4 SAS exome AF: 0.828

Gnomad4 FIN exome AF: 0.823

Gnomad4 NFE exome AF: 0.807

Gnomad4 OTH exome AF: 0.806

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

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.797

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

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

LitVar

Other links and lift over

dbSNP: rs2577138; hg19: chr1-220205980;