rs11702833

Variant names:

• chr21-38588240-C-A
• rs11702833
• ENST00000398919.6:c.-149-3295G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-38588240-C-A
• chr21-38588240-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000398919.6(ERG):​c.-149-3295G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,934 control chromosomes in the GnomAD database, including 8,217 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 0.32 (8217 hom., cov: 32)
• Consequence: ERG ENST00000398919.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 5 publications found

Genes affected

ERG (HGNC:3446): (ETS transcription factor ERG) This gene encodes a member of the erythroblast transformation-specific (ETS) family of transcriptions factors. All members of this family are key regulators of embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis. The protein encoded by this gene is mainly expressed in the nucleus. It contains an ETS DNA-binding domain and a PNT (pointed) domain which is implicated in the self-association of chimeric oncoproteins. This protein is required for platelet adhesion to the subendothelium, inducing vascular cell remodeling. It also regulates hematopoesis, and the differentiation and maturation of megakaryocytic cells. This gene is involved in chromosomal translocations, resulting in different fusion gene products, such as TMPSSR2-ERG and NDRG1-ERG in prostate cancer, EWS-ERG in Ewing's sarcoma and FUS-ERG in acute myeloid leukemia. More than two dozens of transcript variants generated from combinatorial usage of three alternative promoters and multiple alternative splicing events have been reported, but the full-length nature of many of these variants has not been determined. [provided by RefSeq, Apr 2014]

ERG Gene-Disease associations (from GenCC):

• lymphatic malformation 14

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERG	NM_001136154.1	c.-149-3295G>T		intron_variant	Intron 1 of 11		NP_001129626.1
ERG	NM_001243428.1	c.-149-3295G>T		intron_variant	Intron 1 of 11		NP_001230357.1
ERG	NM_004449.4	c.-149-3295G>T		intron_variant	Intron 1 of 10		NP_004440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERG	ENST00000398919.6	c.-149-3295G>T		intron_variant	Intron 1 of 11	1		ENSP00000381891.2
ERG	ENST00000468474.5	n.38-3295G>T		intron_variant	Intron 1 of 7	1
ERG	ENST00000485493.1	n.38-3295G>T		intron_variant	Intron 1 of 4	1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48512 AN: 151814 Hom.: 8210 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.319 AC: 48537 AN: 151934 Hom.: 8217 Cov.: 32 AF XY: 0.313 AC XY: 23258 AN XY: 74248

African (AFR) AF: 0.336 AC: 13918 AN: 41420

American (AMR) AF: 0.237 AC: 3620 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1219 AN: 3468

East Asian (EAS) AF: 0.0413 AC: 214 AN: 5186

South Asian (SAS) AF: 0.223 AC: 1072 AN: 4812

European-Finnish (FIN) AF: 0.316 AC: 3330 AN: 10534

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.353 AC: 23987 AN: 67936

Other (OTH) AF: 0.322 AC: 680 AN: 2110

Alfa AF: 0.330 Hom.: 15904

Bravo AF: 0.313

Asia WGS AF: 0.161 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.031
DANN	Benign	0.56
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11702833; hg19: chr21-39960164; COSMIC: COSV67359909;