21-38624158-A-G

Variant names:

• chr21-38624158-A-G
• rs467207
• ENST00000398919.6:c.-150+36364T>C

Variant summary

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

The ENST00000398919.6(ERG):​c.-150+36364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,058 control chromosomes in the GnomAD database, including 49,702 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 0.81 (49702 hom., cov: 31)
• Consequence: ERG ENST00000398919.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.56
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 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.-150+37500T>C		intron	N/A	NP_001129626.1
	ERG	NM_001243428.1		c.-150+36364T>C		intron	N/A	NP_001230357.1
	ERG	NM_004449.4		c.-150+37500T>C		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.-150+36364T>C		intron	N/A	ENSP00000381891.2
	ERG	ENST00000468474.5	TSL:1	n.37+37500T>C		intron	N/A
	ERG	ENST00000485493.1	TSL:1	n.37+37500T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122395 AN: 151940 Hom.: 49628 Cov.: 31

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.806 AC: 122529 AN: 152058 Hom.: 49702 Cov.: 31 AF XY: 0.804 AC XY: 59758 AN XY: 74306

African (AFR) AF: 0.896 AC: 37174 AN: 41502

American (AMR) AF: 0.772 AC: 11799 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2657 AN: 3466

East Asian (EAS) AF: 0.737 AC: 3788 AN: 5140

South Asian (SAS) AF: 0.789 AC: 3795 AN: 4810

European-Finnish (FIN) AF: 0.739 AC: 7814 AN: 10570

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53005 AN: 67976

Other (OTH) AF: 0.783 AC: 1652 AN: 2110

Alfa AF: 0.790 Hom.: 27803

Bravo AF: 0.812

Asia WGS AF: 0.758 AC: 2638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0020
DANN	Benign	0.20
PhyloP100		-3.6
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: rs467207; hg19: chr21-39996082;