rs2273207
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000125.4(ESR1):c.1369+66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,487,136 control chromosomes in the GnomAD database, including 9,545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.11 ( 1210 hom., cov: 32)
Exomes 𝑓: 0.099 ( 8335 hom. )
Consequence
ESR1
NM_000125.4 intron
NM_000125.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.83
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 6-152061190-A-G is Benign according to our data. Variant chr6-152061190-A-G is described in ClinVar as [Benign]. Clinvar id is 1248080.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESR1 | NM_000125.4 | c.1369+66A>G | intron_variant | ENST00000206249.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESR1 | ENST00000206249.8 | c.1369+66A>G | intron_variant | 1 | NM_000125.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.112 AC: 17063AN: 152032Hom.: 1211 Cov.: 32
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GnomAD4 exome AF: 0.0990 AC: 132165AN: 1334986Hom.: 8335 AF XY: 0.101 AC XY: 67880AN XY: 671280
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GnomAD4 genome ? AF: 0.112 AC: 17074AN: 152150Hom.: 1210 Cov.: 32 AF XY: 0.117 AC XY: 8698AN XY: 74398
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 30, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at