Variant 22-29273704-T-C 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.103-37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,596,820 control chromosomes in the GnomAD database, including 125,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10382 hom., cov: 32)

Exomes 𝑓: 0.40 ( 115316 hom. )

Consequence

EWSR1
NM_005243.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0220

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=-0.85).

BP6

Variant 22-29273704-T-C is Benign according to our data. Variant chr22-29273704-T-C is described in ClinVar as [Benign]. Clinvar id is 1276860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.477 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.103-37T>C		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.103-37T>C		intron_variant		1	NM_005243.4	ENSP00000381031	P4	Q01844-1

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54164

AN:

151992

Hom.:

10383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.446

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.404

Gnomad OTH

AF:

0.392

GnomAD3 exomes

AF:

0.403

AC:

96510

AN:

239494

Hom.:

20302

AF XY:

0.407

AC XY:

52666

AN XY:

129258

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.500

Gnomad ASJ exome

AF:

0.496

Gnomad EAS exome

AF:

0.291

Gnomad SAS exome

AF:

0.457

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.403

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.396

AC:

571428

AN:

1444710

Hom.:

115316

Cov.:

AF XY:

0.399

AC XY:

286382

AN XY:

717818

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.504

Gnomad4 ASJ exome

AF:

0.492

Gnomad4 EAS exome

AF:

0.296

Gnomad4 SAS exome

AF:

0.455

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.394

Gnomad4 OTH exome

AF:

0.401

GnomAD4 genome

AF:

0.356

AC:

54165

AN:

152110

Hom.:

10382

Cov.:

AF XY:

0.361

AC XY:

26849

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.207

Gnomad4 AMR

AF:

0.486

Gnomad4 ASJ

AF:

0.476

Gnomad4 EAS

AF:

0.302

Gnomad4 SAS

AF:

0.446

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.404

Gnomad4 OTH

AF:

0.387

Alfa

AF:

0.407

Hom.:

17620

Bravo

AF:

0.355

Asia WGS

AF:

0.341

AC:

1185

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.2

DANN

Benign

0.36

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