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rs1033182

Variant summary

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

The NM_000125.4(ESR1):c.644-6756G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,122 control chromosomes in the GnomAD database, including 6,367 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 0.26 ( 6367 hom., cov: 32)

Consequence

ESR1
NM_000125.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0790
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=-0.87).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ESR1NM_000125.4 linkuse as main transcriptc.644-6756G>A intron_variant ENST00000206249.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ESR1ENST00000206249.8 linkuse as main transcriptc.644-6756G>A intron_variant 1 NM_000125.4 P1P03372-1

Frequencies

GnomAD3 genomes
AF:
0.256
AC:
38937
AN:
152004
Hom.:
6373
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0680
Gnomad AMI
AF:
0.353
Gnomad AMR
AF:
0.264
Gnomad ASJ
AF:
0.400
Gnomad EAS
AF:
0.0256
Gnomad SAS
AF:
0.216
Gnomad FIN
AF:
0.260
Gnomad MID
AF:
0.392
Gnomad NFE
AF:
0.379
Gnomad OTH
AF:
0.274
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.256
AC:
38926
AN:
152122
Hom.:
6367
Cov.:
32
AF XY:
0.248
AC XY:
18442
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0679
Gnomad4 AMR
AF:
0.265
Gnomad4 ASJ
AF:
0.400
Gnomad4 EAS
AF:
0.0257
Gnomad4 SAS
AF:
0.216
Gnomad4 FIN
AF:
0.260
Gnomad4 NFE
AF:
0.379
Gnomad4 OTH
AF:
0.271
Alfa
AF:
0.304
Hom.:
1005
Bravo
AF:
0.248
Asia WGS
AF:
0.127
AC:
442
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
Cadd
Benign
2.9
Dann
Benign
0.82

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: rs1033182; hg19: chr6-152195034; COSMIC: COSV52800768; API