21-38624158-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.56
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ERGNM_001136154.1 linkuse as main transcriptc.-150+37500T>C intron_variant NP_001129626.1
ERGNM_001243428.1 linkuse as main transcriptc.-150+36364T>C intron_variant NP_001230357.1
ERGNM_001243432.2 linkuse as main transcriptc.-150+37500T>C intron_variant NP_001230361.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ERGENST00000398919.6 linkuse as main transcriptc.-150+36364T>C intron_variant 1 ENSP00000381891 A1P11308-3
ERGENST00000468474.5 linkuse as main transcriptn.37+37500T>C intron_variant, non_coding_transcript_variant 1
ERGENST00000485493.1 linkuse as main transcriptn.37+37500T>C intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.806
AC:
122395
AN:
151940
Hom.:
49628
Cov.:
31
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.896
Gnomad4 AMR
AF:
0.772
Gnomad4 ASJ
AF:
0.767
Gnomad4 EAS
AF:
0.737
Gnomad4 SAS
AF:
0.789
Gnomad4 FIN
AF:
0.739
Gnomad4 NFE
AF:
0.780
Gnomad4 OTH
AF:
0.783
Alfa
AF:
0.790
Hom.:
25131
Bravo
AF:
0.812
Asia WGS
AF:
0.758
AC:
2638
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.0020
DANN
Benign
0.20

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs467207; hg19: chr21-39996082; COSMIC: COSV67395008; API