chr14-100370016-C-T

Position:

• chr14-100370016-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004184.4(WARS1):​c.-73-758G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 151,912 control chromosomes in the GnomAD database, including 37,408 homozygotes. 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: 𝑓 0.69 (37408 hom., cov: 30)
• Consequence: WARS1 NM_004184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.946

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WARS1	NM_004184.4	c.-73-758G>A		intron_variant		ENST00000392882.7	NP_004175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WARS1	ENST00000392882.7	c.-73-758G>A		intron_variant		1	NM_004184.4	ENSP00000376620.2

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104836 AN: 151794 Hom.: 37381 Cov.: 30

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.735

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.691 AC: 104905 AN: 151912 Hom.: 37408 Cov.: 30 AF XY: 0.698 AC XY: 51818 AN XY: 74220

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.738

Alfa AF: 0.735 Hom.: 18848

Bravo AF: 0.686

Asia WGS AF: 0.780 AC: 2714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.45

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: rs941931; hg19: chr14-100836353;