rs979091

Variant names:

• chr21-38425842-C-A
• rs979091
• NM_182918.4:c.237-2281G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-38425842-C-A
• chr21-38425842-C-T

Variant summary

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

The NM_182918.4(ERG):​c.237-2281G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,060 control chromosomes in the GnomAD database, including 34,446 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 0.67 (34446 hom., cov: 33)
• Consequence: ERG NM_182918.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERG	NM_182918.4	c.237-2281G>T		intron_variant	Intron 2 of 9	ENST00000288319.12	NP_891548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERG	ENST00000288319.12	c.237-2281G>T		intron_variant	Intron 2 of 9	1	NM_182918.4	ENSP00000288319.7

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101562 AN: 151942 Hom.: 34418 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.668 AC: 101644 AN: 152060 Hom.: 34446 Cov.: 33 AF XY: 0.664 AC XY: 49356 AN XY: 74314

African (AFR) AF: 0.583 AC: 24165 AN: 41466

American (AMR) AF: 0.603 AC: 9221 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2558 AN: 3468

East Asian (EAS) AF: 0.853 AC: 4407 AN: 5166

South Asian (SAS) AF: 0.684 AC: 3292 AN: 4816

European-Finnish (FIN) AF: 0.663 AC: 7001 AN: 10554

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

European-Non Finnish (NFE) AF: 0.714 AC: 48567 AN: 67990

Other (OTH) AF: 0.672 AC: 1417 AN: 2108

Alfa AF: 0.703 Hom.: 139402

Bravo AF: 0.666

Asia WGS AF: 0.753 AC: 2622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.48
PhyloP100		0.039
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs979091; hg19: chr21-39797764;