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rs9340799

Variant summary

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

The NM_000125.4(ESR1):c.453-351A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,976 control chromosomes in the GnomAD database, including 7,698 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 0.31 ( 7698 hom., cov: 32)

Consequence

ESR1
NM_000125.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.373
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=-0.81).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ESR1NM_000125.4 linkuse as main transcriptc.453-351A>G intron_variant ENST00000206249.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ESR1ENST00000206249.8 linkuse as main transcriptc.453-351A>G intron_variant 1 NM_000125.4 P1P03372-1

Frequencies

GnomAD3 genomes
AF:
0.314
AC:
47759
AN:
151858
Hom.:
7690
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.286
Gnomad AMI
AF:
0.319
Gnomad AMR
AF:
0.287
Gnomad ASJ
AF:
0.386
Gnomad EAS
AF:
0.201
Gnomad SAS
AF:
0.369
Gnomad FIN
AF:
0.233
Gnomad MID
AF:
0.415
Gnomad NFE
AF:
0.351
Gnomad OTH
AF:
0.324
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.315
AC:
47801
AN:
151976
Hom.:
7698
Cov.:
32
AF XY:
0.308
AC XY:
22896
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.286
Gnomad4 AMR
AF:
0.287
Gnomad4 ASJ
AF:
0.386
Gnomad4 EAS
AF:
0.201
Gnomad4 SAS
AF:
0.368
Gnomad4 FIN
AF:
0.233
Gnomad4 NFE
AF:
0.351
Gnomad4 OTH
AF:
0.323
Alfa
AF:
0.335
Hom.:
2554
Bravo
AF:
0.313
Asia WGS
AF:
0.276
AC:
960
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
5.5
Dann
Benign
0.69

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: rs9340799; hg19: chr6-152163381; API