rs1061160

Variant names:

• chr1-219981426-C-T
• rs1061160
• NM_004446.3:c.3405G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_004446.3(EPRS1):​c.3405G>A​(p.Gln1135Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,602,576 control chromosomes in the GnomAD database, including 97,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9512 hom., cov: 32)
  • Exomes 𝑓: 0.35 (88268 hom.)
• Consequence: EPRS1 NM_004446.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.66
• Publications: 24 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 1-219981426-C-T is Benign according to our data. Variant chr1-219981426-C-T is described in ClinVar as Benign. ClinVar VariationId is 1166606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.66 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 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.3405G>A	p.Gln1135Gln	synonymous	Exon 24 of 32	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.3405G>A	p.Gln1135Gln	synonymous	Exon 24 of 32	ENSP00000355890.3	P07814
	EPRS1	ENST00000927912.1		c.3525G>A	p.Gln1175Gln	synonymous	Exon 25 of 33	ENSP00000597971.1
	EPRS1	ENST00000927914.1		c.3450G>A	p.Gln1150Gln	synonymous	Exon 25 of 33	ENSP00000597973.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53761 AN: 151690 Hom.: 9496 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.333

GnomAD2 exomes AF: 0.346 AC: 86312 AN: 249560 AF XY: 0.340

Gnomad AFR exome AF: 0.372

Gnomad AMR exome AF: 0.405

Gnomad ASJ exome AF: 0.268

Gnomad EAS exome AF: 0.396

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.346 AC: 502575 AN: 1450780 Hom.: 88268 Cov.: 31 AF XY: 0.345 AC XY: 248829 AN XY: 721638

African (AFR) AF: 0.381 AC: 12669 AN: 33238

American (AMR) AF: 0.405 AC: 17936 AN: 44242

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 6924 AN: 25906

East Asian (EAS) AF: 0.413 AC: 16341 AN: 39544

South Asian (SAS) AF: 0.302 AC: 25566 AN: 84518

European-Finnish (FIN) AF: 0.313 AC: 16542 AN: 52908

Middle Eastern (MID) AF: 0.382 AC: 2184 AN: 5720

European-Non Finnish (NFE) AF: 0.347 AC: 383738 AN: 1104798

Other (OTH) AF: 0.345 AC: 20675 AN: 59906

GnomAD4 genome AF: 0.355 AC: 53823 AN: 151796 Hom.: 9512 Cov.: 32 AF XY: 0.351 AC XY: 26038 AN XY: 74162

African (AFR) AF: 0.369 AC: 15272 AN: 41374

American (AMR) AF: 0.389 AC: 5947 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 909 AN: 3470

East Asian (EAS) AF: 0.393 AC: 2026 AN: 5156

South Asian (SAS) AF: 0.309 AC: 1484 AN: 4804

European-Finnish (FIN) AF: 0.296 AC: 3102 AN: 10472

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.353 AC: 23947 AN: 67930

Other (OTH) AF: 0.335 AC: 707 AN: 2108

Alfa AF: 0.349 Hom.: 26753

Bravo AF: 0.360

Asia WGS AF: 0.339 AC: 1176 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Leukodystrophy, hypomyelinating, 15 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	7.8
DANN	Benign	0.75
PhyloP100		1.7
Mutation Taster		=95/5	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: rs1061160; hg19: chr1-220154768; COSMIC: COSV65099285; COSMIC: COSV65099285;