ENST00000398919.6:c.39+48082C>T

Variant names:

• chr21-38527580-G-A
• rs1888469
• ENST00000398919.6:c.39+48082C>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+48082C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,062 control chromosomes in the GnomAD database, including 14,973 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 0.43 (14973 hom., cov: 32)
• Consequence: ERG ENST00000398919.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 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+48082C>T		intron	N/A	NP_001129626.1
	ERG	NM_001243428.1		c.39+48082C>T		intron	N/A	NP_001230357.1
	ERG	NM_004449.4		c.39+48082C>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+48082C>T		intron	N/A	ENSP00000381891.2
	ERG	ENST00000468474.5	TSL:1	n.225+48082C>T		intron	N/A
	ERG	ENST00000485493.1	TSL:1	n.225+48082C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65730 AN: 151944 Hom.: 14943 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.433 AC: 65801 AN: 152062 Hom.: 14973 Cov.: 32 AF XY: 0.430 AC XY: 31935 AN XY: 74330

African (AFR) AF: 0.587 AC: 24321 AN: 41448

American (AMR) AF: 0.329 AC: 5025 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1208 AN: 3470

East Asian (EAS) AF: 0.488 AC: 2517 AN: 5158

South Asian (SAS) AF: 0.383 AC: 1844 AN: 4820

European-Finnish (FIN) AF: 0.368 AC: 3892 AN: 10574

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25558 AN: 67988

Other (OTH) AF: 0.429 AC: 907 AN: 2116

Alfa AF: 0.400 Hom.: 23177

Bravo AF: 0.433

Asia WGS AF: 0.427 AC: 1487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0040
DANN	Benign	0.45
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: rs1888469; hg19: chr21-39899504;