rs2836551

Variant names:

• chr21-38600453-T-C
• rs2836551
• ENST00000398919.6:c.-149-15508A>G

Variant summary

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

The ENST00000398919.6(ERG):​c.-149-15508A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,036 control chromosomes in the GnomAD database, including 11,656 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 0.38 (11656 hom., cov: 31)
• Consequence: ERG ENST00000398919.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000398919.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERG	NM_001136154.1		c.-149-15508A>G		intron	N/A	NP_001129626.1
	ERG	NM_001243428.1		c.-149-15508A>G		intron	N/A	NP_001230357.1
	ERG	NM_004449.4		c.-149-15508A>G		intron	N/A	NP_004440.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERG	ENST00000398919.6	TSL:1	c.-149-15508A>G		intron	N/A	ENSP00000381891.2
	ERG	ENST00000468474.5	TSL:1	n.38-15508A>G		intron	N/A
	ERG	ENST00000485493.1	TSL:1	n.38-15508A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58135 AN: 151918 Hom.: 11656 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.382 AC: 58147 AN: 152036 Hom.: 11656 Cov.: 31 AF XY: 0.379 AC XY: 28173 AN XY: 74338

African (AFR) AF: 0.273 AC: 11330 AN: 41468

American (AMR) AF: 0.388 AC: 5927 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1746 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1364 AN: 5126

South Asian (SAS) AF: 0.377 AC: 1817 AN: 4818

European-Finnish (FIN) AF: 0.402 AC: 4248 AN: 10574

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30198 AN: 67980

Other (OTH) AF: 0.402 AC: 849 AN: 2112

Alfa AF: 0.422 Hom.: 40602

Bravo AF: 0.378

Asia WGS AF: 0.309 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.015
DANN	Benign	0.41
PhyloP100		-1.5
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: rs2836551; hg19: chr21-39972377;