ENST00000398919.6:c.39+29033C>T

Variant names:

• chr21-38546629-G-A
• rs2836505
• ENST00000398919.6:c.39+29033C>T

Variant summary

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

The ENST00000398919.6(ERG):​c.39+29033C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,070 control chromosomes in the GnomAD database, including 2,737 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 0.18 (2737 hom., cov: 32)
• Consequence: ERG ENST00000398919.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 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.39+29033C>T		intron	N/A	NP_001129626.1
	ERG	NM_001243428.1		c.39+29033C>T		intron	N/A	NP_001230357.1
	ERG	NM_004449.4		c.39+29033C>T		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.39+29033C>T		intron	N/A	ENSP00000381891.2
	ERG	ENST00000468474.5	TSL:1	n.225+29033C>T		intron	N/A
	ERG	ENST00000485493.1	TSL:1	n.225+29033C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27610 AN: 151952 Hom.: 2730 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.182 AC: 27643 AN: 152070 Hom.: 2737 Cov.: 32 AF XY: 0.186 AC XY: 13824 AN XY: 74336

African (AFR) AF: 0.240 AC: 9966 AN: 41454

American (AMR) AF: 0.148 AC: 2256 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3466

East Asian (EAS) AF: 0.332 AC: 1715 AN: 5160

South Asian (SAS) AF: 0.244 AC: 1176 AN: 4824

European-Finnish (FIN) AF: 0.222 AC: 2352 AN: 10584

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9114 AN: 67986

Other (OTH) AF: 0.176 AC: 370 AN: 2108

Alfa AF: 0.146 Hom.: 5585

Bravo AF: 0.178

Asia WGS AF: 0.275 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.054
DANN	Benign	0.75
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: rs2836505; hg19: chr21-39918553;