rs2234693
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is . The variant received -12 ACMG points: 0P and 12B. BA1BP4_Strong
Benign
The NM_000125.4(ESR1):c.453-397T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.465 (AC=70,725) in the gnomAD database across 152,008 control chromosomes, including 16,806 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.532. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (no review stars).
Frequency
Genomes: 𝑓 0.47 ( 16806 hom., cov: 32)
Consequence
ESR1
NM_000125.4 intron
NM_000125.4 intron
Scores
3
Clinical Significance
Conservation
PhyloP100: 1.18
Publications
608 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: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, Orphanet
Genome browser will be placed here
new If you want to explore the variant's impact on the transcript NM_000125.4, 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 = 0.5325 — exceeds 5%% threshold (BA1 applied)
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000125.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| ESR1 | TSL:1 MANE Select | c.453-397T>C | intron | N/A | ENSP00000206249.3 | P03372-1 | |||
| ESR1 | TSL:1 | c.452+33836T>C | intron | N/A | ENSP00000384064.1 | Q9H2M1 | |||
| ESR1 | TSL:1 | c.-67-397T>C | intron | N/A | ENSP00000394721.2 | P03372-4 |
Frequencies
GnomAD3 genomes 0.465 AC: 70661AN: 151890Hom.: 16789 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
70661
AN:
151890
Hom.:
Cov.:
32
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 0.465 AC: 70725AN: 152008Hom.: 16806 Cov.: 32 AF XY: 0.458 AC XY: 34033AN XY: 74302 show subpopulations
GnomAD4 genome
AF:
AC:
70725
AN:
152008
Hom.:
Cov.:
32
AF XY:
AC XY:
34033
AN XY:
74302
show subpopulations
African (AFR)
AF:
AC:
22314
AN:
41444
American (AMR)
AF:
AC:
5572
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
1586
AN:
3470
East Asian (EAS)
AF:
AC:
2043
AN:
5166
South Asian (SAS)
AF:
AC:
2071
AN:
4814
European-Finnish (FIN)
AF:
AC:
4189
AN:
10560
Middle Eastern (MID)
AF:
AC:
129
AN:
292
European-Non Finnish (NFE)
AF:
AC:
31416
AN:
67968
Other (OTH)
AF:
AC:
940
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
1924
3848
5771
7695
9619
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
640
1280
1920
2560
3200
<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:
1465
AN:
3478
Local populations
ToMMo 61KJPN (+60KJPN MNV)
AF:
AC:
52685
AN:
122742
Turkish Variome
AF:
AC:
724
AN:
1546
Hom.:
WBBC (Westlake BioBank for Chinese) pilot
AF:
AC:
3690
AN:
8960
Hom.:
ABraOM SABE-WGS-1171
AF:
AC:
1043
AN:
2342
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:risk factor
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
-
-
-
Myocardial infarction, susceptibility to (1)
Computational 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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Other links and lift over
dbSNP: rs2234693 ;
hg19: chr6-152163335;