NM_000125.4:c.760+27539T>C

Variant summary

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

The NM_000125.4(ESR1):​c.760+27539T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,046 control chromosomes in the GnomAD database, including 46,183 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 0.77 ( 46183 hom., cov: 31)

Consequence

ESR1
NM_000125.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.39

Publications

12 publications found
Variant links:
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 syndrome
    Inheritance: 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=-0.93).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ESR1NM_000125.4 linkc.760+27539T>C intron_variant Intron 3 of 7 ENST00000206249.8 NP_000116.2 P03372-1G4XH65

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ESR1ENST00000206249.8 linkc.760+27539T>C intron_variant Intron 3 of 7 1 NM_000125.4 ENSP00000206249.3 P03372-1

Frequencies

GnomAD3 genomes
AF:
0.775
AC:
117742
AN:
151928
Hom.:
46148
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.871
Gnomad AMI
AF:
0.852
Gnomad AMR
AF:
0.727
Gnomad ASJ
AF:
0.823
Gnomad EAS
AF:
0.512
Gnomad SAS
AF:
0.608
Gnomad FIN
AF:
0.708
Gnomad MID
AF:
0.803
Gnomad NFE
AF:
0.765
Gnomad OTH
AF:
0.782
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.775
AC:
117831
AN:
152046
Hom.:
46183
Cov.:
31
AF XY:
0.767
AC XY:
56984
AN XY:
74282
show subpopulations
African (AFR)
AF:
0.871
AC:
36162
AN:
41510
American (AMR)
AF:
0.727
AC:
11103
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.823
AC:
2854
AN:
3468
East Asian (EAS)
AF:
0.511
AC:
2641
AN:
5172
South Asian (SAS)
AF:
0.609
AC:
2928
AN:
4808
European-Finnish (FIN)
AF:
0.708
AC:
7462
AN:
10536
Middle Eastern (MID)
AF:
0.822
AC:
240
AN:
292
European-Non Finnish (NFE)
AF:
0.765
AC:
52017
AN:
67956
Other (OTH)
AF:
0.778
AC:
1647
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1305
2611
3916
5222
6527
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
854
1708
2562
3416
4270
<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:
0.772
Hom.:
18172
Bravo
AF:
0.783
Asia WGS
AF:
0.600
AC:
2090
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.065
DANN
Benign
0.35
PhyloP100
-2.4
Mutation Taster
=97/3
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: rs1514347; hg19: chr6-152229445; API