Variant chr22-29273723-C-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.103-18C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 1,597,402 control chromosomes in the GnomAD database, including 4,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 357 hom., cov: 32)

Exomes 𝑓: 0.073 ( 4265 hom. )

Consequence

EWSR1
NM_005243.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.785

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:

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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 22-29273723-C-G is Benign according to our data. Variant chr22-29273723-C-G is described in ClinVar as [Benign]. Clinvar id is 1249698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-29273723-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0847 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.103-18C>G		intron_variant		ENST00000397938.7	NP_005234.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EWSR1	ENST00000397938.7 linkuse as main transcript	c.103-18C>G		intron_variant		1	NM_005243.4	ENSP00000381031	P4	Q01844-1

Frequencies

GnomAD3 genomes

AF:

0.0570

AC:

8650

AN:

151696

Hom.:

357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.0892

Gnomad AMR

AF:

0.0503

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0125

Gnomad FIN

AF:

0.0743

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0865

Gnomad OTH

AF:

0.0518

GnomAD3 exomes

AF:

0.0587

AC:

13946

AN:

237496

Hom.:

566

AF XY:

0.0584

AC XY:

7488

AN XY:

128192

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.0326

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.0000565

Gnomad SAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.0684

Gnomad NFE exome

AF:

0.0869

Gnomad OTH exome

AF:

0.0715

GnomAD4 exome

AF:

0.0725

AC:

104826

AN:

1445590

Hom.:

4265

Cov.:

AF XY:

0.0711

AC XY:

51086

AN XY:

718702

show subpopulations

Gnomad4 AFR exome

AF:

0.0119

Gnomad4 AMR exome

AF:

0.0338

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0154

Gnomad4 FIN exome

AF:

0.0720

Gnomad4 NFE exome

AF:

0.0824

Gnomad4 OTH exome

AF:

0.0640

GnomAD4 genome

AF:

0.0570

AC:

8652

AN:

151812

Hom.:

357

Cov.:

AF XY:

0.0548

AC XY:

4067

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.0143

Gnomad4 AMR

AF:

0.0502

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.0743

Gnomad4 NFE

AF:

0.0865

Gnomad4 OTH

AF:

0.0513

Alfa

AF:

0.0584

Hom.:

Bravo

AF:

0.0542

Asia WGS

AF:

0.0110

AC:

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

0.14

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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