rs9397453

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000125.4(ESR1):​c.761-28429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 152,132 control chromosomes in the GnomAD database, including 394 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 0.045 ( 394 hom., cov: 32)

Consequence

ESR1
NM_000125.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.484
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ESR1NM_000125.4 linkuse as main transcriptc.761-28429G>A intron_variant ENST00000206249.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ESR1ENST00000206249.8 linkuse as main transcriptc.761-28429G>A intron_variant 1 NM_000125.4 P1P03372-1

Frequencies

GnomAD3 genomes
AF:
0.0444
AC:
6756
AN:
152014
Hom.:
386
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.128
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.0191
Gnomad ASJ
AF:
0.0242
Gnomad EAS
AF:
0.0764
Gnomad SAS
AF:
0.0199
Gnomad FIN
AF:
0.0269
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.00340
Gnomad OTH
AF:
0.0325
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0447
AC:
6802
AN:
152132
Hom.:
394
Cov.:
32
AF XY:
0.0446
AC XY:
3314
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.129
Gnomad4 AMR
AF:
0.0191
Gnomad4 ASJ
AF:
0.0242
Gnomad4 EAS
AF:
0.0768
Gnomad4 SAS
AF:
0.0199
Gnomad4 FIN
AF:
0.0269
Gnomad4 NFE
AF:
0.00340
Gnomad4 OTH
AF:
0.0336
Alfa
AF:
0.0211
Hom.:
33
Bravo
AF:
0.0481
Asia WGS
AF:
0.0470
AC:
164
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
3.3
DANN
Benign
0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9397453; hg19: chr6-152236879; API