chr14-100337318-C-A

Position:

• chr14-100337318-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004184.4(WARS1):​c.1114-116G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 1,489,466 control chromosomes in the GnomAD database, including 454,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43682 hom., cov: 32)
  • Exomes 𝑓: 0.78 (411027 hom.)
• Consequence: WARS1 NM_004184.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.32

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-100337318-C-A is Benign according to our data. Variant chr14-100337318-C-A is described in ClinVar as [Benign]. Clinvar id is 1267941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WARS1	NM_004184.4	c.1114-116G>T		intron_variant		ENST00000392882.7	NP_004175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WARS1	ENST00000392882.7	c.1114-116G>T		intron_variant		1	NM_004184.4	ENSP00000376620.2

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114452 AN: 152006 Hom.: 43646 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.784

GnomAD4 exome AF: 0.783 AC: 1046847 AN: 1337342 Hom.: 411027 AF XY: 0.785 AC XY: 516479 AN XY: 658318

Gnomad4 AFR exome AF: 0.626

Gnomad4 AMR exome AF: 0.872

Gnomad4 ASJ exome AF: 0.837

Gnomad4 EAS exome AF: 0.879

Gnomad4 SAS exome AF: 0.836

Gnomad4 FIN exome AF: 0.816

Gnomad4 NFE exome AF: 0.774

Gnomad4 OTH exome AF: 0.787

GnomAD4 genome AF: 0.753 AC: 114540 AN: 152124 Hom.: 43682 Cov.: 32 AF XY: 0.758 AC XY: 56336 AN XY: 74356

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.786

Alfa AF: 0.700 Hom.: 2171

Bravo AF: 0.750

Asia WGS AF: 0.835 AC: 2906 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.91
CADD	Benign	0.14
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs2234528; hg19: chr14-100803655;