chr14-100376300-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong
The NM_173701.2(WARS1):c.-114G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000438 in 1,028,376 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000049 ( 0 hom. )
Consequence
WARS1
NM_173701.2 5_prime_UTR
NM_173701.2 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.17
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]
WDR25 (HGNC:21064): (WD repeat domain 25) This gene encodes a protein containing 7 WD repeats. WD repeats are approximately 30 to 40-amino acid domains containing several conserved residues, typically having a Tryptophan-Aspartic acid dipeptide (WD) at the C-terminal end. WD domains are involved in protein-protein interactions in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_173701.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| WARS1 | NM_173701.2 | c.-114G>A | 5_prime_UTR | Exon 1 of 11 | NP_776049.1 | P23381-1 | |||
| WARS1 | NM_213645.2 | c.-65G>A | 5_prime_UTR | Exon 1 of 10 | NP_998810.1 | P23381-2 | |||
| WDR25 | NM_001161476.3 | MANE Select | c.-211C>T | upstream_gene | N/A | NP_001154948.1 | A0A384NPW5 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| WARS1 | ENST00000355338.6 | TSL:1 | c.-114G>A | 5_prime_UTR | Exon 1 of 11 | ENSP00000347495.2 | P23381-1 | ||
| WARS1 | ENST00000883283.1 | c.-244G>A | 5_prime_UTR | Exon 1 of 12 | ENSP00000553342.1 | ||||
| WARS1 | ENST00000883284.1 | c.-77G>A | 5_prime_UTR | Exon 1 of 11 | ENSP00000553343.1 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152206
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000491 AC: 43AN: 876052Hom.: 0 Cov.: 12 AF XY: 0.0000598 AC XY: 25AN XY: 417928 show subpopulations
GnomAD4 exome
AF:
AC:
43
AN:
876052
Hom.:
Cov.:
12
AF XY:
AC XY:
25
AN XY:
417928
show subpopulations
African (AFR)
AF:
AC:
0
AN:
19438
American (AMR)
AF:
AC:
0
AN:
7864
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
12892
East Asian (EAS)
AF:
AC:
0
AN:
25086
South Asian (SAS)
AF:
AC:
0
AN:
14676
European-Finnish (FIN)
AF:
AC:
0
AN:
20306
Middle Eastern (MID)
AF:
AC:
0
AN:
2512
European-Non Finnish (NFE)
AF:
AC:
43
AN:
736442
Other (OTH)
AF:
AC:
0
AN:
36836
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.0000131 AC: 2AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74484 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152324
Hom.:
Cov.:
33
AF XY:
AC XY:
2
AN XY:
74484
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41580
American (AMR)
AF:
AC:
0
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68016
Other (OTH)
AF:
AC:
0
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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