chr1-220008242-T-C

Variant names:

• chr1-220008242-T-C
• rs7545314
• NM_004446.3:c.1606-904A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004446.3(EPRS1):​c.1606-904A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,054 control chromosomes in the GnomAD database, including 49,548 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 0.81 (49548 hom., cov: 32)
• Consequence: EPRS1 NM_004446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 4 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPRS1	NM_004446.3	MANE Select	c.1606-904A>G		intron	N/A	NP_004437.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPRS1	ENST00000366923.8	TSL:1 MANE Select	c.1606-904A>G		intron	N/A	ENSP00000355890.3
	EPRS1	ENST00000609181.5	TSL:1	c.1627-904A>G		intron	N/A	ENSP00000477245.1
	EPRS1	ENST00000477030.2	TSL:1	n.*631+2704A>G		intron	N/A	ENSP00000477493.1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122495 AN: 151936 Hom.: 49508 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.798

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.806 AC: 122586 AN: 152054 Hom.: 49548 Cov.: 32 AF XY: 0.808 AC XY: 60031 AN XY: 74328

African (AFR) AF: 0.776 AC: 32154 AN: 41430

American (AMR) AF: 0.849 AC: 12983 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2501 AN: 3470

East Asian (EAS) AF: 0.929 AC: 4814 AN: 5182

South Asian (SAS) AF: 0.836 AC: 4038 AN: 4830

European-Finnish (FIN) AF: 0.818 AC: 8624 AN: 10548

Middle Eastern (MID) AF: 0.781 AC: 228 AN: 292

European-Non Finnish (NFE) AF: 0.807 AC: 54852 AN: 67986

Other (OTH) AF: 0.799 AC: 1687 AN: 2112

Alfa AF: 0.809 Hom.: 11974

Bravo AF: 0.806

Asia WGS AF: 0.890 AC: 3093 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.020
DANN	Benign	0.77
PhyloP100		-1.7
Mutation Taster		=100/0	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: rs7545314; hg19: chr1-220181584;