rs465327

Variant names:

• chr21-38646547-G-A
• rs465327
• ENST00000398919.6:c.-150+13975C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-38646547-G-A
• chr21-38646547-G-C
• chr21-38646547-G-T

Variant summary

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

The NM_001136154.1(ERG):​c.-150+15111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 152,076 control chromosomes in the GnomAD database, including 51,008 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 0.82 (51008 hom., cov: 31)
• Consequence: ERG NM_001136154.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 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.-150+15111C>T		intron	N/A	NP_001129626.1
	ERG	NM_001243428.1		c.-150+13975C>T		intron	N/A	NP_001230357.1
	ERG	NM_004449.4		c.-150+15111C>T		intron	N/A	NP_004440.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERG	ENST00000398919.6	TSL:1	c.-150+13975C>T		intron	N/A	ENSP00000381891.2
	ERG	ENST00000468474.5	TSL:1	n.37+15111C>T		intron	N/A
	ERG	ENST00000485493.1	TSL:1	n.37+15111C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123867 AN: 151956 Hom.: 50943 Cov.: 31

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.815 AC: 123993 AN: 152076 Hom.: 51008 Cov.: 31 AF XY: 0.813 AC XY: 60395 AN XY: 74306

African (AFR) AF: 0.937 AC: 38896 AN: 41526

American (AMR) AF: 0.778 AC: 11889 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2876 AN: 3468

East Asian (EAS) AF: 0.737 AC: 3789 AN: 5144

South Asian (SAS) AF: 0.811 AC: 3914 AN: 4826

European-Finnish (FIN) AF: 0.726 AC: 7656 AN: 10552

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52297 AN: 67962

Other (OTH) AF: 0.786 AC: 1658 AN: 2110

Alfa AF: 0.799 Hom.: 5941

Bravo AF: 0.824

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.45
DANN	Benign	0.64
PhyloP100		-0.25
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: rs465327; hg19: chr21-40018471;