GeneBe

rs104893956

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000427531.6(ESR1):​c.-51C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

ESR1
ENST00000427531.6 5_prime_UTR_premature_start_codon_gain

Scores

3
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.06

Publications

0 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

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ESR1NM_000125.4 linkc.469C>G p.Arg157Gly missense_variant Exon 2 of 8 ENST00000206249.8 NP_000116.2 P03372-1G4XH65

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ESR1ENST00000206249.8 linkc.469C>G p.Arg157Gly missense_variant Exon 2 of 8 1 NM_000125.4 ENSP00000206249.3 P03372-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Uncertain
0.053
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T;T;T;T
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.96
.;.;D;.
M_CAP
Benign
0.034
D
MetaRNN
Pathogenic
0.75
D;D;D;D
MetaSVM
Benign
-0.88
T
MutationAssessor
Uncertain
2.5
M;M;M;M
PhyloP100
3.1
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.3
N;N;N;N
REVEL
Uncertain
0.36
Sift
Benign
0.035
D;D;D;D
Sift4G
Benign
0.20
T;T;T;T
Polyphen
1.0
D;D;D;D
Vest4
0.54
MutPred
0.71
Loss of stability (P = 0.0475);Loss of stability (P = 0.0475);Loss of stability (P = 0.0475);Loss of stability (P = 0.0475);
MVP
0.66
MPC
1.0
ClinPred
0.92
D
GERP RS
6.0
Varity_R
0.18
gMVP
0.42
Mutation Taster
=235/65
polymorphism

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: rs104893956; hg19: chr6-152163748; API