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rs2234693

Variant summary

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

The NM_000125.4(ESR1):c.453-397T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,008 control chromosomes in the GnomAD database, including 16,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.47 ( 16806 hom., cov: 32)

Consequence

ESR1
NM_000125.4 intron

Scores

2

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 1.18
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 (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ESR1NM_000125.4 linkuse as main transcriptc.453-397T>C intron_variant ENST00000206249.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ESR1ENST00000206249.8 linkuse as main transcriptc.453-397T>C intron_variant 1 NM_000125.4 P1P03372-1

Frequencies

GnomAD3 genomes
AF:
0.465
AC:
70661
AN:
151890
Hom.:
16789
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.538
Gnomad AMI
AF:
0.510
Gnomad AMR
AF:
0.365
Gnomad ASJ
AF:
0.457
Gnomad EAS
AF:
0.396
Gnomad SAS
AF:
0.432
Gnomad FIN
AF:
0.397
Gnomad MID
AF:
0.452
Gnomad NFE
AF:
0.462
Gnomad OTH
AF:
0.443
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.465
AC:
70725
AN:
152008
Hom.:
16806
Cov.:
32
AF XY:
0.458
AC XY:
34033
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.538
Gnomad4 AMR
AF:
0.365
Gnomad4 ASJ
AF:
0.457
Gnomad4 EAS
AF:
0.395
Gnomad4 SAS
AF:
0.430
Gnomad4 FIN
AF:
0.397
Gnomad4 NFE
AF:
0.462
Gnomad4 OTH
AF:
0.445
Alfa
AF:
0.449
Hom.:
6385
Bravo
AF:
0.462
Asia WGS
AF:
0.422
AC:
1465
AN:
3478

ClinVar

Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Myocardial infarction, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMNov 05, 2003- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
4.3
Dann
Benign
0.68

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: rs2234693; hg19: chr6-152163335; API