rs3788410

chr22-29274950-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005243.4(EWSR1):c.226+1086T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,128 control chromosomes in the GnomAD database, including 9,834 homozygotes. 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 0.34 (9834 hom., cov: 32)
• Consequence: EWSR1 NM_005243.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EWSR1	NM_005243.4	c.226+1086T>C		intron_variant		ENST00000397938.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EWSR1	ENST00000397938.7	c.226+1086T>C		intron_variant		1	NM_005243.4	P4

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51758 AN: 152010 Hom.: 9837 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.379

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.340 AC: 51751 AN: 152128 Hom.: 9834 Cov.: 32 AF XY: 0.345 AC XY: 25661 AN XY: 74356

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.375

Alfa AF: 0.377 Hom.: 1988

Bravo AF: 0.338

Asia WGS AF: 0.327 AC: 1137 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.4
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs3788410; hg19: chr22-29670939; COSMIC: COSV58425103; COSMIC: COSV58425103;