Variant 14-100342389-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004184.4(WARS1):c.1113+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00726 in 1,613,364 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 57 hom. )

Consequence

WARS1
NM_004184.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.377

Variant links:

Genes affected

WARS1 (HGNC:12729): (tryptophanyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Two forms of tryptophanyl-tRNA synthetase exist, a cytoplasmic form, named WARS, and a mitochondrial form, named WARS2. Tryptophanyl-tRNA synthetase (WARS) catalyzes the aminoacylation of tRNA(trp) with tryptophan and is induced by interferon. Tryptophanyl-tRNA synthetase belongs to the class I tRNA synthetase family. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

WARS1 links:

WARS1 (HGNC:):

WARS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-100342389-A-G is Benign according to our data. Variant chr14-100342389-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2644530.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 984 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WARS1	NM_004184.4 linkuse as main transcript	c.1113+9T>C		intron_variant		ENST00000392882.7	NP_004175.2	P23381-1A0A024R6K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WARS1	ENST00000392882.7 linkuse as main transcript	c.1113+9T>C		intron_variant		1	NM_004184.4	ENSP00000376620.2		P23381-1

Frequencies

GnomAD3 genomes

AF:

0.00647

AC:

984

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.0736

Gnomad AMR

AF:

0.00786

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00928

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00662

AC:

1663

AN:

251118

Hom.:

AF XY:

0.00705

AC XY:

957

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00535

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00320

Gnomad FIN exome

AF:

0.00292

Gnomad NFE exome

AF:

0.00983

Gnomad OTH exome

AF:

0.00833

GnomAD4 exome

AF:

0.00735

AC:

10735

AN:

1461204

Hom.:

Cov.:

AF XY:

0.00749

AC XY:

5447

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.00494

Gnomad4 ASJ exome

AF:

0.0132

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00331

Gnomad4 FIN exome

AF:

0.00281

Gnomad4 NFE exome

AF:

0.00824

Gnomad4 OTH exome

AF:

0.00691

GnomAD4 genome

AF:

0.00647

AC:

984

AN:

152160

Hom.:

Cov.:

AF XY:

0.00668

AC XY:

497

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00785

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00928

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00911

Hom.:

Bravo

AF:

0.00669

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0112

EpiControl

AF:

0.0116

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

WARS1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0050

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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