Variant 22-29292643-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005243.4(EWSR1):c.1164+37T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,368,836 control chromosomes in the GnomAD database, including 21,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1665 hom., cov: 32)

Exomes 𝑓: 0.17 ( 19398 hom. )

Consequence

EWSR1
NM_005243.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.51

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 links:

EWSR1 (HGNC:):

EWSR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 22-29292643-T-G is Benign according to our data. Variant chr22-29292643-T-G is described in ClinVar as [Benign]. Clinvar id is 1280213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EWSR1	NM_005243.4 linkuse as main transcript	c.1164+37T>G		intron_variant		ENST00000397938.7	NP_005234.1	Q01844-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EWSR1	ENST00000397938.7 linkuse as main transcript	c.1164+37T>G		intron_variant		1	NM_005243.4	ENSP00000381031.2		Q01844-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19710

AN:

152090

Hom.:

1668

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0326

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.140

GnomAD3 exomes

AF:

0.185

AC:

45709

AN:

247646

Hom.:

4861

AF XY:

0.191

AC XY:

25589

AN XY:

133890

show subpopulations

Gnomad AFR exome

AF:

0.0288

Gnomad AMR exome

AF:

0.242

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.197

Gnomad SAS exome

AF:

0.297

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.169

GnomAD4 exome

AF:

0.171

AC:

207886

AN:

1216628

Hom.:

19398

Cov.:

AF XY:

0.175

AC XY:

107043

AN XY:

613058

show subpopulations

Gnomad4 AFR exome

AF:

0.0270

Gnomad4 AMR exome

AF:

0.226

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.291

Gnomad4 FIN exome

AF:

0.199

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.162

GnomAD4 genome

AF:

0.129

AC:

19702

AN:

152208

Hom.:

1665

Cov.:

AF XY:

0.135

AC XY:

10020

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0325

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.197

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.144

Hom.:

1919

Bravo

AF:

0.121

Asia WGS

AF:

0.257

AC:

897

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over