chr6-151958743-G-A

Variant summary

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

The NM_000125.4(ESR1):​c.1096+14235G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,022 control chromosomes in the GnomAD database, including 24,940 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 0.55 ( 24940 hom., cov: 32)

Consequence

ESR1
NM_000125.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.266

Publications

13 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=-0.91).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ESR1NM_000125.4 linkc.1096+14235G>A intron_variant Intron 4 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.1096+14235G>A intron_variant Intron 4 of 7 1 NM_000125.4 ENSP00000206249.3 P03372-1

Frequencies

GnomAD3 genomes
AF:
0.548
AC:
83274
AN:
151902
Hom.:
24941
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.308
Gnomad AMI
AF:
0.715
Gnomad AMR
AF:
0.559
Gnomad ASJ
AF:
0.664
Gnomad EAS
AF:
0.389
Gnomad SAS
AF:
0.431
Gnomad FIN
AF:
0.668
Gnomad MID
AF:
0.709
Gnomad NFE
AF:
0.683
Gnomad OTH
AF:
0.593
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.548
AC:
83299
AN:
152022
Hom.:
24940
Cov.:
32
AF XY:
0.545
AC XY:
40520
AN XY:
74306
show subpopulations
African (AFR)
AF:
0.308
AC:
12746
AN:
41418
American (AMR)
AF:
0.559
AC:
8537
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.664
AC:
2302
AN:
3468
East Asian (EAS)
AF:
0.388
AC:
2007
AN:
5168
South Asian (SAS)
AF:
0.433
AC:
2090
AN:
4826
European-Finnish (FIN)
AF:
0.668
AC:
7055
AN:
10564
Middle Eastern (MID)
AF:
0.724
AC:
213
AN:
294
European-Non Finnish (NFE)
AF:
0.683
AC:
46453
AN:
67982
Other (OTH)
AF:
0.589
AC:
1244
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1748
3495
5243
6990
8738
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
704
1408
2112
2816
3520
<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:
0.611
Hom.:
6235
Bravo
AF:
0.527
Asia WGS
AF:
0.411
AC:
1433
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.66
DANN
Benign
0.67
PhyloP100
-0.27
Mutation Taster
=100/0
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: rs3020396; hg19: chr6-152279878; API