rs1256049
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001437.3(ESR2):c.984G>A(p.Val328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 1,613,366 control chromosomes in the GnomAD database, including 4,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.066 ( 675 hom., cov: 31)
Exomes 𝑓: 0.044 ( 3351 hom. )
Consequence
ESR2
NM_001437.3 synonymous
NM_001437.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0340
Genes affected
ESR2 (HGNC:3468): (estrogen receptor 2) This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
Variant 14-64257333-C-T is Benign according to our data. Variant chr14-64257333-C-T is described in ClinVar as [Benign]. Clinvar id is 1228925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.034 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ESR2 | NM_001437.3 | c.984G>A | p.Val328= | synonymous_variant | 6/9 | ENST00000341099.6 | NP_001428.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ESR2 | ENST00000341099.6 | c.984G>A | p.Val328= | synonymous_variant | 6/9 | 1 | NM_001437.3 | ENSP00000343925 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0661 AC: 10050AN: 152108Hom.: 674 Cov.: 31
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GnomAD3 exomes AF: 0.0667 AC: 16779AN: 251436Hom.: 1557 AF XY: 0.0624 AC XY: 8474AN XY: 135902
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GnomAD4 exome AF: 0.0445 AC: 64963AN: 1461140Hom.: 3351 Cov.: 31 AF XY: 0.0438 AC XY: 31842AN XY: 726868
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GnomAD4 genome AF: 0.0662 AC: 10080AN: 152226Hom.: 675 Cov.: 31 AF XY: 0.0687 AC XY: 5112AN XY: 74410
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | This variant is associated with the following publications: (PMID: 11231990) - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
ESR2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 22, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at