rs2836496

Variant names:

• chr21-38542589-A-C
• rs2836496
• ENST00000398919.6:c.39+33073T>G

Your query was ambiguous. Multiple possible variants found:

• chr21-38542589-A-C
• chr21-38542589-A-G

Variant summary

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

The NM_001136154.1(ERG):​c.39+33073T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,136 control chromosomes in the GnomAD database, including 2,460 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 0.17 (2460 hom., cov: 32)
• Consequence: ERG NM_001136154.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364
• Publications: 0 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

ENSG00000287470 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136154.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERG	NM_001136154.1		c.39+33073T>G		intron	N/A	NP_001129626.1	P11308-3
	ERG	NM_001243428.1		c.39+33073T>G		intron	N/A	NP_001230357.1	P11308-3
	ERG	NM_004449.4		c.39+33073T>G		intron	N/A	NP_004440.1	P11308-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERG	ENST00000398919.6	TSL:1	c.39+33073T>G		intron	N/A	ENSP00000381891.2	P11308-3
	ERG	ENST00000468474.5	TSL:1	n.225+33073T>G		intron	N/A
	ERG	ENST00000485493.1	TSL:1	n.225+33073T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26320 AN: 152018 Hom.: 2456 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.173 AC: 26355 AN: 152136 Hom.: 2460 Cov.: 32 AF XY: 0.177 AC XY: 13142 AN XY: 74392

African (AFR) AF: 0.246 AC: 10187 AN: 41492

American (AMR) AF: 0.143 AC: 2190 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3468

East Asian (EAS) AF: 0.211 AC: 1090 AN: 5178

South Asian (SAS) AF: 0.178 AC: 856 AN: 4820

European-Finnish (FIN) AF: 0.205 AC: 2167 AN: 10578

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8868 AN: 68008

Other (OTH) AF: 0.151 AC: 318 AN: 2104

Alfa AF: 0.140 Hom.: 6771

Bravo AF: 0.173

Asia WGS AF: 0.179 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	10
DANN	Benign	0.70
PhyloP100		0.36
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: rs2836496; hg19: chr21-39914513;