rs1570305

Variant names:

• chr14-100341818-G-A
• rs1570305
• NM_004184.4:c.1113+580C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• distal hereditary motor neuropathy

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: G2P, ClinGen
• neuronopathy, distal hereditary motor, type 9

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Broad Center for Mendelian Genomics, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ENSG00000258666 (HGNC:58289):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004184.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WARS1	NM_004184.4	MANE Select	c.1113+580C>T		intron	N/A	NP_004175.2
	WARS1	NM_173701.2		c.1113+580C>T		intron	N/A	NP_776049.1
	WARS1	NM_213645.2		c.990+580C>T		intron	N/A	NP_998810.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WARS1	ENST00000392882.7	TSL:1 MANE Select	c.1113+580C>T		intron	N/A	ENSP00000376620.2
	WARS1	ENST00000355338.6	TSL:1	c.1113+580C>T		intron	N/A	ENSP00000347495.2
	WARS1	ENST00000557135.5	TSL:1	c.1113+580C>T		intron	N/A	ENSP00000451460.1

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

African (AFR) AF: 0.588 AC: 24386 AN: 41464

American (AMR) AF: 0.838 AC: 12810 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2921 AN: 3472

East Asian (EAS) AF: 0.865 AC: 4478 AN: 5176

South Asian (SAS) AF: 0.837 AC: 4040 AN: 4826

European-Finnish (FIN) AF: 0.812 AC: 8594 AN: 10590

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52876 AN: 68020

Other (OTH) AF: 0.777 AC: 1637 AN: 2108

Alfa AF: 0.719 Hom.: 3863

Bravo AF: 0.736

Asia WGS AF: 0.830 AC: 2889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.41
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1570305; hg19: chr14-100808155;