chr22-29281978-C-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005243.4(EWSR1):​c.414-412C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,186 control chromosomes in the GnomAD database, including 1,888 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 0.15 ( 1888 hom., cov: 32)

Consequence

EWSR1
NM_005243.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0470

Publications

5 publications found
Variant links:
Genes affected
EWSR1 (HGNC:3508): (EWS RNA binding protein 1) This gene encodes a multifunctional protein that is involved in various cellular processes, including gene expression, cell signaling, and RNA processing and transport. The protein includes an N-terminal transcriptional activation domain and a C-terminal RNA-binding domain. Chromosomal translocations between this gene and various genes encoding transcription factors result in the production of chimeric proteins that are involved in tumorigenesis. These chimeric proteins usually consist of the N-terminal transcriptional activation domain of this protein fused to the C-terminal DNA-binding domain of the transcription factor protein. Mutations in this gene, specifically a t(11;22)(q24;q12) translocation, are known to cause Ewing sarcoma as well as neuroectodermal and various other tumors. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1 and 14. [provided by RefSeq, Jul 2009]
EWSR1 Gene-Disease associations (from GenCC):
  • amyotrophic lateral sclerosis
    Inheritance: Unknown, AD Classification: MODERATE, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EWSR1NM_005243.4 linkc.414-412C>A intron_variant Intron 5 of 16 ENST00000397938.7 NP_005234.1 Q01844-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EWSR1ENST00000397938.7 linkc.414-412C>A intron_variant Intron 5 of 16 1 NM_005243.4 ENSP00000381031.2 Q01844-1

Frequencies

GnomAD3 genomes
AF:
0.151
AC:
22914
AN:
152068
Hom.:
1886
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.108
Gnomad AMI
AF:
0.146
Gnomad AMR
AF:
0.107
Gnomad ASJ
AF:
0.180
Gnomad EAS
AF:
0.279
Gnomad SAS
AF:
0.0765
Gnomad FIN
AF:
0.214
Gnomad MID
AF:
0.139
Gnomad NFE
AF:
0.171
Gnomad OTH
AF:
0.142
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.151
AC:
22942
AN:
152186
Hom.:
1888
Cov.:
32
AF XY:
0.148
AC XY:
11030
AN XY:
74398
show subpopulations
African (AFR)
AF:
0.108
AC:
4478
AN:
41524
American (AMR)
AF:
0.107
AC:
1637
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.180
AC:
624
AN:
3472
East Asian (EAS)
AF:
0.281
AC:
1453
AN:
5180
South Asian (SAS)
AF:
0.0781
AC:
377
AN:
4830
European-Finnish (FIN)
AF:
0.214
AC:
2266
AN:
10572
Middle Eastern (MID)
AF:
0.136
AC:
40
AN:
294
European-Non Finnish (NFE)
AF:
0.171
AC:
11628
AN:
68000
Other (OTH)
AF:
0.145
AC:
306
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1000
2000
3000
4000
5000
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
242
484
726
968
1210
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.153
Hom.:
950
Bravo
AF:
0.143
Asia WGS
AF:
0.166
AC:
577
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
4.0
DANN
Benign
0.72
PhyloP100
-0.047
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

Publications

Other links and lift over

dbSNP: rs5752899; hg19: chr22-29677967; API