1-220005980-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.1950+126T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 542,448 control chromosomes in the GnomAD database, including 179,172 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 (49044 hom., cov: 30)
  • Exomes 𝑓: 0.81 (130128 hom.)
• Consequence: EPRS1 NM_004446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337

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=-1.0).
• 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.1950+126T>A		intron_variant		ENST00000366923.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPRS1	ENST00000366923.8	c.1950+126T>A		intron_variant		1	NM_004446.3	P1
EPRS1	ENST00000609181.5	c.1971+126T>A		intron_variant		1
EPRS1	ENST00000477030.2	c.*632-620T>A		intron_variant, NMD_transcript_variant		1
EPRS1	ENST00000464052.5	n.372+126T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121774 AN: 151820 Hom.: 49005 Cov.: 30

Gnomad AFR AF: 0.760

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: 0.790

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.796

GnomAD4 exome AF: 0.814 AC: 318069 AN: 390510 Hom.: 130128 AF XY: 0.814 AC XY: 165552 AN XY: 203448

Gnomad4 AFR exome AF: 0.764

Gnomad4 AMR exome AF: 0.867

Gnomad4 ASJ exome AF: 0.732

Gnomad4 EAS exome AF: 0.920

Gnomad4 SAS exome AF: 0.827

Gnomad4 FIN exome AF: 0.822

Gnomad4 NFE exome AF: 0.807

Gnomad4 OTH exome AF: 0.802

GnomAD4 genome AF: 0.802 AC: 121867 AN: 151938 Hom.: 49044 Cov.: 30 AF XY: 0.804 AC XY: 59691 AN XY: 74260

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.796

Alfa AF: 0.805 Hom.: 6118

Bravo AF: 0.801

Asia WGS AF: 0.888 AC: 3087 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.90
Dann	Benign	0.43

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

LitVar

Other links and lift over

dbSNP: rs2647420; hg19: chr1-220179322;