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rs9371564

Variant summary

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

The NM_000125.4(ESR1):c.761-3195A>G 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 152,064 control chromosomes in the GnomAD database, including 24,459 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 ( 24459 hom., cov: 33)

Consequence

ESR1
NM_000125.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.103
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=-0.92).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ESR1NM_000125.4 linkuse as main transcriptc.761-3195A>G intron_variant ENST00000206249.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ESR1ENST00000206249.8 linkuse as main transcriptc.761-3195A>G intron_variant 1 NM_000125.4 P1P03372-1

Frequencies

GnomAD3 genomes
AF:
0.548
AC:
83242
AN:
151946
Hom.:
24465
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.360
Gnomad AMI
AF:
0.766
Gnomad AMR
AF:
0.509
Gnomad ASJ
AF:
0.720
Gnomad EAS
AF:
0.291
Gnomad SAS
AF:
0.405
Gnomad FIN
AF:
0.669
Gnomad MID
AF:
0.715
Gnomad NFE
AF:
0.668
Gnomad OTH
AF:
0.577
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.548
AC:
83263
AN:
152064
Hom.:
24459
Cov.:
33
AF XY:
0.543
AC XY:
40354
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.360
Gnomad4 AMR
AF:
0.509
Gnomad4 ASJ
AF:
0.720
Gnomad4 EAS
AF:
0.291
Gnomad4 SAS
AF:
0.407
Gnomad4 FIN
AF:
0.669
Gnomad4 NFE
AF:
0.668
Gnomad4 OTH
AF:
0.572
Alfa
AF:
0.630
Hom.:
6438
Bravo
AF:
0.524
Asia WGS
AF:
0.353
AC:
1232
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
Cadd
Benign
3.6
Dann
Benign
0.53

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: rs9371564; hg19: chr6-152262113; API