rs1570305

Positions:

• chr14-100341818-G-A
• chr14-100341818-G-C
• chr14-100341818-G-T

Variant summary

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

The NM_004184.4(WARS1):​c.1113+580C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,142 control chromosomes in the GnomAD database, including 42,493 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 0.74 (42493 hom., cov: 32)
• Consequence: WARS1 NM_004184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WARS1	NM_004184.4	c.1113+580C>T		intron_variant		ENST00000392882.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WARS1	ENST00000392882.7	c.1113+580C>T		intron_variant		1	NM_004184.4	P1
	ENST00000557226.1	n.114+7915G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112521 AN: 152024 Hom.: 42461 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.740 AC: 112599 AN: 152142 Hom.: 42493 Cov.: 32 AF XY: 0.745 AC XY: 55402 AN XY: 74384

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.777

Alfa AF: 0.729 Hom.: 3740

Bravo AF: 0.736

Asia WGS AF: 0.830 AC: 2889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.41

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: rs1570305; hg19: chr14-100808155;