1-216623420-G-T
Variant names:
Variant summary
Our verdict is . The variant received -12 ACMG points: 0P and 12B. BA1BP4_Strong
Benign
The NM_001438.4(ESRRG):c.589+27553C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.423 (AC=64,208) in the gnomAD database across 151,858 control chromosomes, including 14,661 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.59. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.42 ( 14661 hom., cov: 31)
Consequence
ESRRG
NM_001438.4 intron
NM_001438.4 intron
Scores
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.469
Publications
4 publications found
Genes affected
ESRRG (HGNC:3474): (estrogen related receptor gamma) This gene encodes a member of the estrogen receptor-related receptor (ESRR) family, which belongs to the nuclear hormone receptor superfamily. All members of the ESRR family share an almost identical DNA binding domain, which is composed of two C4-type zinc finger motifs. The ESRR members are orphan nuclear receptors; they bind to the estrogen response element and steroidogenic factor 1 response element, and activate genes controlled by both response elements in the absence of any ligands. The ESRR family is closely related to the estrogen receptor (ER) family. They share target genes, co-regulators and promoters, and by targeting the same set of genes, the ESRRs seem to interfere with the ER-mediated estrogen response in various ways. It has been reported that the family member encoded by this gene functions as a transcriptional activator of DNA cytosine-5-methyltransferases 1 (Dnmt1) expression by direct binding to its response elements in the DNMT1 promoters, modulates cell proliferation and estrogen signaling in breast cancer, and negatively regulates bone morphogenetic protein 2-induced osteoblast differentiation and bone formation. Multiple alternatively spliced transcript variants have been identified, which mainly differ at the 5' end and some of which encode protein isoforms differing in the N-terminal region. [provided by RefSeq, Aug 2011]
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new If you want to explore the variant's impact on the transcript NM_001438.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
Classification according to ACMG Germline Pathogenicity v2019
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
BA1
GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.5902 — exceeds 5%% threshold (BA1 applied)
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001438.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ESRRG | TSL:1 MANE Select | c.589+27553C>A | intron | N/A | ENSP00000386171.3 | P62508-1 | |||
| ESRRG | TSL:1 | c.604+27553C>A | intron | N/A | ENSP00000355904.1 | P62508-5 | |||
| ESRRG | TSL:1 | c.520+27553C>A | intron | N/A | ENSP00000352077.2 | P62508-2 |
Frequencies
GnomAD3 genomes 0.423 AC: 64147AN: 151740Hom.: 14638 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
64147
AN:
151740
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.423 AC: 64208AN: 151858Hom.: 14661 Cov.: 31 AF XY: 0.424 AC XY: 31448AN XY: 74214 show subpopulations
GnomAD4 genome
AF:
AC:
64208
AN:
151858
Hom.:
Cov.:
31
AF XY:
AC XY:
31448
AN XY:
74214
show subpopulations
African (AFR)
AF:
AC:
24688
AN:
41392
American (AMR)
AF:
AC:
6358
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
1361
AN:
3470
East Asian (EAS)
AF:
AC:
2711
AN:
5148
South Asian (SAS)
AF:
AC:
1849
AN:
4812
European-Finnish (FIN)
AF:
AC:
3880
AN:
10536
Middle Eastern (MID)
AF:
AC:
95
AN:
294
European-Non Finnish (NFE)
AF:
AC:
22087
AN:
67916
Other (OTH)
AF:
AC:
875
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1798
3597
5395
7194
8992
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
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30-35
35-40
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Age
Alfa
AF:
Hom.:
Bravo
AF:
Local populations
ToMMo 61KJPN (+60KJPN MNV)
AF:
AC:
68840
AN:
122794
Turkish Variome
AF:
AC:
538
AN:
1546
Hom.:
WBBC (Westlake BioBank for Chinese) pilot
AF:
AC:
4731
AN:
8960
Hom.:
ABraOM SABE-WGS-1171
AF:
AC:
993
AN:
2342
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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