Variant 22-29268434-G-A 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.13+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,611,450 control chromosomes in the GnomAD database, including 103,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9457 hom., cov: 33)

Exomes 𝑓: 0.35 ( 93837 hom. )

Consequence

EWSR1
NM_005243.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.205

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=-0.84).

BP6

Variant 22-29268434-G-A is Benign according to our data. Variant chr22-29268434-G-A is described in ClinVar as [Benign]. Clinvar id is 1246240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 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.13+85G>A		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.13+85G>A		intron_variant		1	NM_005243.4	ENSP00000381031	P4	Q01844-1

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52378

AN:

152018

Hom.:

9428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.335

Gnomad EAS

AF:

0.651

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.306

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.329

GnomAD4 exome

AF:

0.352

AC:

513354

AN:

1459316

Hom.:

93837

AF XY:

0.353

AC XY:

256028

AN XY:

726008

show subpopulations

Gnomad4 AFR exome

AF:

0.324

Gnomad4 AMR exome

AF:

0.358

Gnomad4 ASJ exome

AF:

0.332

Gnomad4 EAS exome

AF:

0.657

Gnomad4 SAS exome

AF:

0.429

Gnomad4 FIN exome

AF:

0.395

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.345

AC:

52454

AN:

152134

Hom.:

9457

Cov.:

AF XY:

0.349

AC XY:

25931

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.335

Gnomad4 EAS

AF:

0.652

Gnomad4 SAS

AF:

0.448

Gnomad4 FIN

AF:

0.389

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.337

Alfa

AF:

0.332

Hom.:

2805

Bravo

AF:

0.337

Asia WGS

AF:

0.567

AC:

1973

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

-0.84

CADD

Benign

5.9

DANN

Benign

0.87

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