rs1131692059
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000125.4(ESR1):c.1181G>A(p.Arg394His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Consequence
NM_000125.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESR1 | NM_000125.4 | c.1181G>A | p.Arg394His | missense_variant | 5/8 | ENST00000206249.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESR1 | ENST00000206249.8 | c.1181G>A | p.Arg394His | missense_variant | 5/8 | 1 | NM_000125.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461180Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726900
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Estrogen resistance syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 03, 2018 | - - |
Likely pathogenic, no assertion criteria provided | literature only | SIB Swiss Institute of Bioinformatics | Mar 24, 2017 | The variant is absent from the ExAC database, it consegregates with disease phenotype, it is highly conserved and located in the steroid binding region of the estrogen receptor. It is predicted to be disease causing by MutationTaster. Functional studies show decreased estrogen receptor activity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at