rs2647420

Variant names:

• chr1-220005980-A-C
• rs2647420
• NM_004446.3:c.1950+126T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-220005980-A-C
• chr1-220005980-A-G
• chr1-220005980-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004446.3(EPRS1):​c.1950+126T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPRS1 NM_004446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPRS1	NM_004446.3	c.1950+126T>G		intron_variant	Intron 15 of 31	ENST00000366923.8	NP_004437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPRS1	ENST00000366923.8	c.1950+126T>G		intron_variant	Intron 15 of 31	1	NM_004446.3	ENSP00000355890.3
EPRS1	ENST00000609181.5	c.1971+126T>G		intron_variant	Intron 16 of 20	1		ENSP00000477245.1
EPRS1	ENST00000477030.2	n.*632-620T>G		intron_variant	Intron 10 of 11	1		ENSP00000477493.1
EPRS1	ENST00000464052.5	n.372+126T>G		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 391396 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 203910

African (AFR) AF: 0.00 AC: 0 AN: 10476

American (AMR) AF: 0.00 AC: 0 AN: 11514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10910

East Asian (EAS) AF: 0.00 AC: 0 AN: 25180

South Asian (SAS) AF: 0.00 AC: 0 AN: 23120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 256462

Other (OTH) AF: 0.00 AC: 0 AN: 21098

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.93
DANN	Benign	0.17
PhyloP100		-0.34

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: rs2647420; hg19: chr1-220179322;