rs189387468

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005243.4(EWSR1):c.582-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0038 in 1,589,418 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 18 hom. )

Consequence

EWSR1
NM_005243.4 intron

Scores

Splicing: ADA: 0.00008784

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0550

Publications

0 publications found

Variant links:

COSMIC-nc: COSV105202265

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

EWSR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 22-29286914-C-G is Benign according to our data. Variant chr22-29286914-C-G is described in ClinVar as [Benign]. Clinvar id is 773619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 457 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EWSR1	NM_005243.4 link	c.582-9C>G		intron_variant	Intron 6 of 16	ENST00000397938.7	NP_005234.1	Q01844-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EWSR1	ENST00000397938.7 link	c.582-9C>G		intron_variant	Intron 6 of 16	1	NM_005243.4	ENSP00000381031.2		Q01844-1

Frequencies

GnomAD3 genomes

AF:

0.00304

AC:

457

AN:

150542

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000953

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00398

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00199

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.00475

Gnomad OTH

AF:

0.00386

GnomAD2 exomes

AF:

0.00283

AC:

684

AN:

241320

AF XY:

0.00285

show subpopulations

Gnomad AFR exome

AF:

0.000565

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00104

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00187

Gnomad NFE exome

AF:

0.00440

Gnomad OTH exome

AF:

0.00430

GnomAD4 exome

AF:

0.00388

AC:

5589

AN:

1438764

Hom.:

Cov.:

AF XY:

0.00386

AC XY:

2761

AN XY:

715956

show subpopulations

African (AFR)

AF:

0.000555

AC:

AN:

32436

American (AMR)

AF:

0.00355

AC:

149

AN:

41920

Ashkenazi Jewish (ASJ)

AF:

0.00102

AC:

AN:

25598

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39524

South Asian (SAS)

AF:

0.000335

AC:

AN:

83602

European-Finnish (FIN)

AF:

0.00158

AC:

AN:

53202

Middle Eastern (MID)

AF:

0.00423

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.00455

AC:

4993

AN:

1097386

Other (OTH)

AF:

0.00448

AC:

266

AN:

59428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

271

541

812

1082

1353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00303

AC:

457

AN:

150654

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

207

AN XY:

73492

show subpopulations

African (AFR)

AF:

0.000950

AC:

AN:

41050

American (AMR)

AF:

0.00397

AC:

AN:

15104

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.000209

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00199

AC:

AN:

10074

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00475

AC:

322

AN:

67750

Other (OTH)

AF:

0.00382

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00296

Hom.:

Bravo

AF:

0.00315

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ewing sarcoma

Benign:1

Apr 08, 2019

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.6

(source)

DANN

Benign

0.49

PhyloP100

-0.055

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000088

dbscSNV1_RF

Benign

0.0080

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs189387468

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over