rs2647449

chr1-220003621-A-G

Variant summary

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

The NM_004446.3(EPRS1):c.2063+1627T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,152 control chromosomes in the GnomAD database, including 49,732 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 (49732 hom., cov: 33)
• Consequence: EPRS1 NM_004446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-1.02).
• 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.2063+1627T>C		intron_variant		ENST00000366923.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPRS1	ENST00000366923.8	c.2063+1627T>C		intron_variant		1	NM_004446.3	P1
EPRS1	ENST00000609181.5	c.2084+1627T>C		intron_variant		1
EPRS1	ENST00000477030.2	c.*744+1627T>C		intron_variant, NMD_transcript_variant		1
EPRS1	ENST00000464052.5	n.485+1627T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122760 AN: 152034 Hom.: 49693 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.837

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: 0.807 AC: 122852 AN: 152152 Hom.: 49732 Cov.: 33 AF XY: 0.809 AC XY: 60137 AN XY: 74354

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.799

Alfa AF: 0.815 Hom.: 8551

Bravo AF: 0.807

Asia WGS AF: 0.890 AC: 3094 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	2.2
Dann	Benign	0.66

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: rs2647449; hg19: chr1-220176963;