rs9340973
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_000125.4(ESR1):c.1097-95A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000895 in 1,417,048 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0046 ( 5 hom., cov: 31)
Exomes 𝑓: 0.00045 ( 6 hom. )
Consequence
ESR1
NM_000125.4 intron
NM_000125.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.115
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BP6
?
Variant 6-152011561-A-G is Benign according to our data. Variant chr6-152011561-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1254013.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESR1 | NM_000125.4 | c.1097-95A>G | intron_variant | ENST00000206249.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESR1 | ENST00000206249.8 | c.1097-95A>G | intron_variant | 1 | NM_000125.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00461 AC: 701AN: 152198Hom.: 5 Cov.: 31
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GnomAD4 exome AF: 0.000449 AC: 568AN: 1264732Hom.: 6 AF XY: 0.000372 AC XY: 238AN XY: 639650
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GnomAD4 genome ? AF: 0.00460 AC: 700AN: 152316Hom.: 5 Cov.: 31 AF XY: 0.00450 AC XY: 335AN XY: 74468
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 22, 2019 | - - |
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