rs2301291

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

10 publications found

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:

RHBDD3 (HGNC:1308): (rhomboid domain containing 3) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within several processes, including liver development; negative regulation of natural killer cell activation; and positive regulation of protein catabolic process. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

RHBDD3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005243.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EWSR1	NM_005243.4	MANE Select	c.13+85G>A	intron	N/A	NP_005234.1	Q01844-1
EWSR1	NM_001438500.1		c.13+85G>A	intron	N/A	NP_001425429.1
EWSR1	NM_001438528.1		c.13+85G>A	intron	N/A	NP_001425457.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EWSR1	ENST00000397938.7	TSL:1 MANE Select	c.13+85G>A	intron	N/A	ENSP00000381031.2	Q01844-1
EWSR1	ENST00000406548.5	TSL:1	c.13+85G>A	intron	N/A	ENSP00000385726.1	Q01844-3
EWSR1	ENST00000332050.10	TSL:1	c.13+85G>A	intron	N/A	ENSP00000330896.7	C9JGE3

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

African (AFR)

AF:

0.324

AC:

10833

AN:

33454

American (AMR)

AF:

0.358

AC:

15979

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

8675

AN:

26118

East Asian (EAS)

AF:

0.657

AC:

26087

AN:

39690

South Asian (SAS)

AF:

0.429

AC:

37019

AN:

86234

European-Finnish (FIN)

AF:

0.395

AC:

20462

AN:

51856

Middle Eastern (MID)

AF:

0.322

AC:

1845

AN:

5736

European-Non Finnish (NFE)

AF:

0.334

AC:

371397

AN:

1111218

Other (OTH)

AF:

0.349

AC:

21057

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

17995

35990

53985

71980

89975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12230

24460

36690

48920

61150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.345

AC:

52454

AN:

152134

Hom.:

9457

Cov.:

AF XY:

0.349

AC XY:

25931

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.326

AC:

13516

AN:

41510

American (AMR)

AF:

0.303

AC:

4637

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

1164

AN:

3470

East Asian (EAS)

AF:

0.652

AC:

3364

AN:

5160

South Asian (SAS)

AF:

0.448

AC:

2160

AN:

4822

European-Finnish (FIN)

AF:

0.389

AC:

4116

AN:

10584

Middle Eastern (MID)

AF:

0.298

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.331

AC:

22505

AN:

67966

Other (OTH)

AF:

0.337

AC:

711

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1785

3570

5356

7141

8926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

516

1032

1548

2064

2580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.340

Hom.:

5834

Bravo

AF:

0.337

Asia WGS

AF:

0.567

AC:

1973

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.9

(source)

DANN

Benign

0.87

PhyloP100

0.20

PromoterAI

-0.044

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over