rs1555345959
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The ENST00000509242.5(ESRRB):c.1505dup(p.His503AlafsTer40) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
ESRRB
ENST00000509242.5 frameshift, splice_region
ENST00000509242.5 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.518
Genes affected
ESRRB (HGNC:3473): (estrogen related receptor beta) This gene encodes a protein with similarity to the estrogen receptor. Its function is unknown; however, a similar protein in mouse plays an essential role in placental development. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0164 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESRRB | NM_001379180.1 | c.*2241dup | 3_prime_UTR_variant | 7/7 | ENST00000644823.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESRRB | ENST00000644823.1 | c.*2241dup | 3_prime_UTR_variant | 7/7 | NM_001379180.1 | P1 | |||
ENST00000554926.1 | n.414+1460_414+1461insT | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461576Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727082
GnomAD4 exome
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3
AN:
1461576
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30
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2
AN XY:
727082
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 08, 2016 | Variant classified as Uncertain Significance - Favor Pathogenic. The p.His503fs variant in ESRRB has not been previously reported in individuals with hearing lo ss or in large population studies. This variant is located in the last exon and is predicted to cause a frameshift. It is predicted to alter the protein?s amin o acid sequence beginning at position 503 and lead to a termination codon 40 ami no acids downstream from the canonical termination codon, thus resulting in a pr otein 34 amino acids longer than the normal one. Therefore, the impact of this variant on the protein function is unknown. In summary, while there is some sus picion for a pathogenic role, the clinical significance of the p.His503fs varian t is uncertain. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at