chr6-151916483-G-T

Variant summary

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

The NM_000125.4(ESR1):​c.761-27690G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,004 control chromosomes in the GnomAD database, including 28,637 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 0.61 ( 28637 hom., cov: 32)

Consequence

ESR1
NM_000125.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.355

Publications

16 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=-0.87).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ESR1NM_000125.4 linkc.761-27690G>T 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.761-27690G>T intron_variant Intron 3 of 7 1 NM_000125.4 ENSP00000206249.3 P03372-1

Frequencies

GnomAD3 genomes
AF:
0.607
AC:
92167
AN:
151886
Hom.:
28620
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.521
Gnomad AMI
AF:
0.775
Gnomad AMR
AF:
0.533
Gnomad ASJ
AF:
0.765
Gnomad EAS
AF:
0.403
Gnomad SAS
AF:
0.469
Gnomad FIN
AF:
0.654
Gnomad MID
AF:
0.750
Gnomad NFE
AF:
0.682
Gnomad OTH
AF:
0.629
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.607
AC:
92237
AN:
152004
Hom.:
28637
Cov.:
32
AF XY:
0.601
AC XY:
44626
AN XY:
74312
show subpopulations
African (AFR)
AF:
0.521
AC:
21593
AN:
41434
American (AMR)
AF:
0.532
AC:
8132
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.765
AC:
2655
AN:
3472
East Asian (EAS)
AF:
0.402
AC:
2076
AN:
5158
South Asian (SAS)
AF:
0.471
AC:
2265
AN:
4808
European-Finnish (FIN)
AF:
0.654
AC:
6921
AN:
10576
Middle Eastern (MID)
AF:
0.765
AC:
225
AN:
294
European-Non Finnish (NFE)
AF:
0.682
AC:
46341
AN:
67964
Other (OTH)
AF:
0.627
AC:
1325
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
1803
3606
5409
7212
9015
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
760
1520
2280
3040
3800
<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:
0.672
Hom.:
15222
Bravo
AF:
0.592
Asia WGS
AF:
0.462
AC:
1607
AN:
3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
2.6
DANN
Benign
0.64
PhyloP100
-0.35
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: rs4870062; hg19: chr6-152237618; API