Variant 22-29286914-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005243.4(EWSR1):c.582-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EWSR1
NM_005243.4 intron

Scores

Splicing: ADA: 0.00001815

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0550

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 Likely_benign. Variant got -4 ACMG points.

BP4

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

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150510

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000199

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000269

AC:

AN:

241320

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

130514

show subpopulations

Gnomad AFR exome

AF:

0.000314

Gnomad AMR exome

AF:

0.000276

Gnomad ASJ exome

AF:

0.000415

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.000175

Gnomad FIN exome

AF:

0.0000937

Gnomad NFE exome

AF:

0.000301

Gnomad OTH exome

AF:

0.000688

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000654

AC:

AN:

1437838

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

715470

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.000791

Gnomad4 ASJ exome

AF:

0.000235

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000132

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000328

Gnomad4 OTH exome

AF:

0.0000842

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000133

AC:

AN:

150510

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000199

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00122

Hom.:

EpiCase

AF:

0.00

EpiControl

AF:

0.000179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.7

DANN

Benign

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over