1-219968681-C-T

Position:

• chr1-219968681-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004446.3(EPRS1):​c.*125G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 879,570 control chromosomes in the GnomAD database, including 99,194 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 0.46 (16212 hom., cov: 33)
  • Exomes 𝑓: 0.48 (82982 hom.)
• Consequence: EPRS1 NM_004446.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPRS1	NM_004446.3	c.*125G>A		3_prime_UTR_variant	32/32	ENST00000366923.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPRS1	ENST00000366923.8	c.*125G>A		3_prime_UTR_variant	32/32	1	NM_004446.3	P1
EPRS1	ENST00000468487.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69960 AN: 151910 Hom.: 16206 Cov.: 33

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.476 AC: 345987 AN: 727544 Hom.: 82982 Cov.: 10 AF XY: 0.476 AC XY: 177001 AN XY: 372080

Gnomad4 AFR exome AF: 0.416

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.480

Gnomad4 SAS exome AF: 0.523

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.460 AC: 70003 AN: 152026 Hom.: 16212 Cov.: 33 AF XY: 0.464 AC XY: 34502 AN XY: 74320

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.464

Alfa AF: 0.457 Hom.: 3982

Bravo AF: 0.447

Asia WGS AF: 0.549 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.37

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: rs1061248; hg19: chr1-220142023; COSMIC: COSV65097269; COSMIC: COSV65097269;