Variant chr1-219981426-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004446.3(EPRS1):c.3405G>A(p.Gln1135=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.66

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPRS1	NM_004446.3 linkuse as main transcript	c.3405G>A	p.Gln1135=	synonymous_variant	24/32	ENST00000366923.8	NP_004437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPRS1	ENST00000366923.8 linkuse as main transcript	c.3405G>A	p.Gln1135=	synonymous_variant	24/32	1	NM_004446.3	ENSP00000355890	P1

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53761

AN:

151690

Hom.:

9496

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.346

AC:

86312

AN:

249560

Hom.:

15186

AF XY:

0.340

AC XY:

45868

AN XY:

134944

show subpopulations

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 SAS exome

AF:

0.302

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.:

AF XY:

0.345

AC XY:

248829

AN XY:

721638

show subpopulations

Gnomad4 AFR exome

AF:

0.381

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.313

Gnomad4 NFE exome

AF:

0.347

Gnomad4 OTH exome

AF:

0.345

GnomAD4 genome

AF:

0.355

AC:

53823

AN:

151796

Hom.:

9512

Cov.:

AF XY:

0.351

AC XY:

26038

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.369

Gnomad4 AMR

AF:

0.389

Gnomad4 ASJ

AF:

0.262

Gnomad4 EAS

AF:

0.393

Gnomad4 SAS

AF:

0.309

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.353

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.346

Hom.:

18068

Bravo

AF:

0.360

Asia WGS

AF:

0.339

AC:

1176

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Leukodystrophy, hypomyelinating, 15

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

7.8

DANN

Benign

0.75

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over