rs3853248
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000125.4(ESR1):c.452+10387T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,790 control chromosomes in the GnomAD database, including 4,867 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 0.23 ( 4867 hom., cov: 31)
Consequence
ESR1
NM_000125.4 intron
NM_000125.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.978
Publications
16 publications found
Genes affected
ESR1 (HGNC:3467): (estrogen receptor 1) This gene encodes an estrogen receptor and ligand-activated transcription factor. The canonical protein contains an N-terminal ligand-independent transactivation domain, a central DNA binding domain, a hinge domain, and a C-terminal ligand-dependent transactivation domain. The protein localizes to the nucleus where it may form either a homodimer or a heterodimer with estrogen receptor 2. The protein encoded by this gene regulates the transcription of many estrogen-inducible genes that play a role in growth, metabolism, sexual development, gestation, and other reproductive functions and is expressed in many non-reproductive tissues. The receptor encoded by this gene plays a key role in breast cancer, endometrial cancer, and osteoporosis. This gene is reported to have dozens of transcript variants due to the use of alternate promoters and alternative splicing, however, the full-length nature of many of these variants remain uncertain. [provided by RefSeq, Jul 2020]
ESR1 Gene-Disease associations (from GenCC):
- estrogen resistance syndromeInheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
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=-0.84).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.226 AC: 34210AN: 151674Hom.: 4851 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
34210
AN:
151674
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 AF: 0.226 AC: 34266AN: 151790Hom.: 4867 Cov.: 31 AF XY: 0.228 AC XY: 16931AN XY: 74196 show subpopulations
GnomAD4 genome
AF:
AC:
34266
AN:
151790
Hom.:
Cov.:
31
AF XY:
AC XY:
16931
AN XY:
74196
show subpopulations
African (AFR)
AF:
AC:
16741
AN:
41284
American (AMR)
AF:
AC:
3616
AN:
15248
Ashkenazi Jewish (ASJ)
AF:
AC:
515
AN:
3468
East Asian (EAS)
AF:
AC:
1510
AN:
5160
South Asian (SAS)
AF:
AC:
1063
AN:
4812
European-Finnish (FIN)
AF:
AC:
1702
AN:
10544
Middle Eastern (MID)
AF:
AC:
17
AN:
292
European-Non Finnish (NFE)
AF:
AC:
8526
AN:
67960
Other (OTH)
AF:
AC:
448
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
1210
2421
3631
4842
6052
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
342
684
1026
1368
1710
<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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1015
AN:
3478
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
Publications
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