14-100337405-C-G

Position:

• chr14-100337405-C-G

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.1114-203G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,082 control chromosomes in the GnomAD database, including 2,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.17 (2417 hom., cov: 30)
• Consequence: WARS1 NM_004184.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.286

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-100337405-C-G is Benign according to our data. Variant chr14-100337405-C-G is described in ClinVar as [Benign]. Clinvar id is 1269460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WARS1	NM_004184.4	c.1114-203G>C		intron_variant		ENST00000392882.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WARS1	ENST00000392882.7	c.1114-203G>C		intron_variant		1	NM_004184.4	P1
	ENST00000557226.1	n.114+3502C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25531 AN: 151964 Hom.: 2419 Cov.: 30

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.168 AC: 25521 AN: 152082 Hom.: 2417 Cov.: 30 AF XY: 0.165 AC XY: 12289 AN XY: 74324

Gnomad4 AFR AF: 0.0964

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.161

Alfa AF: 0.111 Hom.: 187

Bravo AF: 0.161

Asia WGS AF: 0.141 AC: 491 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.43

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: rs11622361; hg19: chr14-100803742;