chr6-151807928-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000125.4(ESR1):c.16C>T(p.His6Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0045 in 1,613,882 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. H6H) has been classified as Likely benign.
Frequency
Consequence
NM_000125.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESR1 | NM_000125.4 | c.16C>T | p.His6Tyr | missense_variant | 1/8 | ENST00000206249.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESR1 | ENST00000206249.8 | c.16C>T | p.His6Tyr | missense_variant | 1/8 | 1 | NM_000125.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00309 AC: 470AN: 152198Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00327 AC: 811AN: 248082Hom.: 2 AF XY: 0.00323 AC XY: 435AN XY: 134520
GnomAD4 exome AF: 0.00465 AC: 6791AN: 1461566Hom.: 23 Cov.: 30 AF XY: 0.00449 AC XY: 3266AN XY: 727092
GnomAD4 genome ? AF: 0.00308 AC: 469AN: 152316Hom.: 1 Cov.: 32 AF XY: 0.00273 AC XY: 203AN XY: 74468
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | ESR1: PP3, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 30, 2019 | Identified in an individual with primary ovarian insufficiency, however, functional studies in HEK293T cells demonstrated that the variant showed similar transcriptional activity to wild type (Bouilly et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 23074960, 27603904) - |
ESR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 27, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at