chr1-219983387-C-T

Variant names:

• chr1-219983387-C-T
• rs5030754
• NM_004446.3:c.3102G>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.3102G>A​(p.Lys1034Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 1,605,802 control chromosomes in the GnomAD database, including 7,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1366 hom., cov: 33)
  • Exomes 𝑓: 0.087 (6328 hom.)
• Consequence: EPRS1 NM_004446.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.05
• Publications: 11 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=-0.24).
• BP6: Variant 1-219983387-C-T is Benign according to our data. Variant chr1-219983387-C-T is described in ClinVar as Benign. ClinVar VariationId is 1166607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 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.3102G>A	p.Lys1034Lys	synonymous	Exon 22 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.3102G>A	p.Lys1034Lys	synonymous	Exon 22 of 32	ENSP00000355890.3	P07814
	EPRS1	ENST00000927912.1		c.3222G>A	p.Lys1074Lys	synonymous	Exon 23 of 33	ENSP00000597971.1
	EPRS1	ENST00000927914.1		c.3147G>A	p.Lys1049Lys	synonymous	Exon 23 of 33	ENSP00000597973.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18031 AN: 152130 Hom.: 1365 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0767

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0619

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.0798 AC: 19772 AN: 247864 AF XY: 0.0765

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.0493

Gnomad ASJ exome AF: 0.0315

Gnomad EAS exome AF: 0.0637

Gnomad FIN exome AF: 0.0675

Gnomad NFE exome AF: 0.0903

Gnomad OTH exome AF: 0.0816

GnomAD4 exome AF: 0.0870 AC: 126456 AN: 1453554 Hom.: 6328 Cov.: 31 AF XY: 0.0849 AC XY: 61384 AN XY: 723168

African (AFR) AF: 0.229 AC: 7587 AN: 33156

American (AMR) AF: 0.0542 AC: 2400 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.0324 AC: 843 AN: 26020

East Asian (EAS) AF: 0.0602 AC: 2385 AN: 39616

South Asian (SAS) AF: 0.0349 AC: 2974 AN: 85334

European-Finnish (FIN) AF: 0.0721 AC: 3847 AN: 53382

Middle Eastern (MID) AF: 0.0683 AC: 392 AN: 5740

European-Non Finnish (NFE) AF: 0.0911 AC: 100702 AN: 1105902

Other (OTH) AF: 0.0886 AC: 5326 AN: 60134

GnomAD4 genome AF: 0.119 AC: 18066 AN: 152248 Hom.: 1366 Cov.: 33 AF XY: 0.113 AC XY: 8415 AN XY: 74454

African (AFR) AF: 0.217 AC: 9008 AN: 41516

American (AMR) AF: 0.0766 AC: 1172 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3470

East Asian (EAS) AF: 0.0628 AC: 325 AN: 5176

South Asian (SAS) AF: 0.0414 AC: 200 AN: 4828

European-Finnish (FIN) AF: 0.0619 AC: 657 AN: 10620

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0922 AC: 6269 AN: 68022

Other (OTH) AF: 0.102 AC: 216 AN: 2112

Alfa AF: 0.102 Hom.: 465

Bravo AF: 0.125

Asia WGS AF: 0.0580 AC: 202 AN: 3478

EpiCase AF: 0.0916

EpiControl AF: 0.0867

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	6.7
DANN	Benign	0.76
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5030754; hg19: chr1-220156729; COSMIC: COSV65099293; COSMIC: COSV65099293;