chr21-38397191-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182918.4(ERG):​c.745+3383A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,042 control chromosomes in the GnomAD database, including 5,823 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 0.26 ( 5823 hom., cov: 31)

Consequence

ERG
NM_182918.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.809

Publications

3 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ERGNM_182918.4 linkc.745+3383A>G intron_variant Intron 6 of 9 ENST00000288319.12 NP_891548.1 P11308-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ERGENST00000288319.12 linkc.745+3383A>G intron_variant Intron 6 of 9 1 NM_182918.4 ENSP00000288319.7 P11308-4

Frequencies

GnomAD3 genomes
AF:
0.258
AC:
39151
AN:
151924
Hom.:
5814
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0970
Gnomad AMI
AF:
0.408
Gnomad AMR
AF:
0.335
Gnomad ASJ
AF:
0.277
Gnomad EAS
AF:
0.268
Gnomad SAS
AF:
0.365
Gnomad FIN
AF:
0.271
Gnomad MID
AF:
0.215
Gnomad NFE
AF:
0.325
Gnomad OTH
AF:
0.268
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.258
AC:
39189
AN:
152042
Hom.:
5823
Cov.:
31
AF XY:
0.258
AC XY:
19206
AN XY:
74308
show subpopulations
African (AFR)
AF:
0.0973
AC:
4035
AN:
41488
American (AMR)
AF:
0.335
AC:
5121
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.277
AC:
962
AN:
3468
East Asian (EAS)
AF:
0.269
AC:
1385
AN:
5156
South Asian (SAS)
AF:
0.364
AC:
1752
AN:
4816
European-Finnish (FIN)
AF:
0.271
AC:
2867
AN:
10566
Middle Eastern (MID)
AF:
0.221
AC:
65
AN:
294
European-Non Finnish (NFE)
AF:
0.325
AC:
22056
AN:
67958
Other (OTH)
AF:
0.272
AC:
574
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1400
2800
4199
5599
6999
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
408
816
1224
1632
2040
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.187
Hom.:
667
Bravo
AF:
0.254
Asia WGS
AF:
0.320
AC:
1113
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
0.068
DANN
Benign
0.51
PhyloP100
-0.81
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

Publications

Other links and lift over

dbSNP: rs2836368; hg19: chr21-39769113; API