Variant 14-100335086-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004184.4(WARS1):c.1255-50A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,591,454 control chromosomes in the GnomAD database, including 784,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70827 hom., cov: 32)

Exomes 𝑓: 1.0 ( 713454 hom. )

Consequence

WARS1
NM_004184.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.46

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 14-100335086-T-C is Benign according to our data. Variant chr14-100335086-T-C is described in ClinVar as [Benign]. Clinvar id is 1251090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WARS1	NM_004184.4 linkuse as main transcript	c.1255-50A>G		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.1255-50A>G		intron_variant		1	NM_004184.4	ENSP00000376620.2		P23381-1

Frequencies

GnomAD3 genomes

AF:

0.963

AC:

146502

AN:

152148

Hom.:

70776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.979

Gnomad ASJ

AF:

0.993

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.972

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.973

GnomAD3 exomes

AF:

0.989

AC:

235284

AN:

237862

Hom.:

116495

AF XY:

0.992

AC XY:

127780

AN XY:

128862

show subpopulations

Gnomad AFR exome

AF:

0.874

Gnomad AMR exome

AF:

0.992

Gnomad ASJ exome

AF:

0.993

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.998

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.991

GnomAD4 exome

AF:

0.996

AC:

1432734

AN:

1439188

Hom.:

713454

Cov.:

AF XY:

0.996

AC XY:

710438

AN XY:

713350

show subpopulations

Gnomad4 AFR exome

AF:

0.871

Gnomad4 AMR exome

AF:

0.991

Gnomad4 ASJ exome

AF:

0.993

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.998

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.990

GnomAD4 genome

AF:

0.963

AC:

146611

AN:

152266

Hom.:

70827

Cov.:

AF XY:

0.964

AC XY:

71765

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.876

Gnomad4 AMR

AF:

0.979

Gnomad4 ASJ

AF:

0.993

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.973

Alfa

AF:

0.989

Hom.:

8562

Bravo

AF:

0.958

Asia WGS

AF:

0.991

AC:

3446

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.5

DANN

Benign

0.34

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