Menu
GeneBe

22-29286941-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005243.4(EWSR1):c.600G>A(p.Pro200=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,611,102 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

EWSR1
NM_005243.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.224
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-29286941-G-A is Benign according to our data. Variant chr22-29286941-G-A is described in ClinVar as [Benign]. Clinvar id is 724658.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.224 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 153 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EWSR1NM_005243.4 linkuse as main transcriptc.600G>A p.Pro200= synonymous_variant 7/17 ENST00000397938.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EWSR1ENST00000397938.7 linkuse as main transcriptc.600G>A p.Pro200= synonymous_variant 7/171 NM_005243.4 P4Q01844-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00102
AC:
153
AN:
149724
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000198
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00215
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00379
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00108
Gnomad OTH
AF:
0.000977
GnomAD3 exomes
AF:
0.00133
AC:
333
AN:
251142
Hom.:
0
AF XY:
0.00136
AC XY:
184
AN XY:
135718
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.00286
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00356
Gnomad NFE exome
AF:
0.00130
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.00141
AC:
2059
AN:
1461274
Hom.:
2
Cov.:
33
AF XY:
0.00140
AC XY:
1019
AN XY:
726960
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.00253
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00318
Gnomad4 NFE exome
AF:
0.00153
Gnomad4 OTH exome
AF:
0.00116
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00102
AC:
153
AN:
149828
Hom.:
1
Cov.:
32
AF XY:
0.00103
AC XY:
75
AN XY:
73018
show subpopulations
Gnomad4 AFR
AF:
0.000197
Gnomad4 AMR
AF:
0.00214
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00379
Gnomad4 NFE
AF:
0.00108
Gnomad4 OTH
AF:
0.000966
Alfa
AF:
0.00108
Hom.:
0
Bravo
AF:
0.00110
EpiCase
AF:
0.00125
EpiControl
AF:
0.00148

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
10
Dann
Benign
0.63

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146607451; hg19: chr22-29682930; API