rs534216019
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001379180.1(ESRRB):c.689-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000867 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000088 ( 0 hom. )
Consequence
ESRRB
NM_001379180.1 splice_polypyrimidine_tract, intron
NM_001379180.1 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00005467
2
Clinical Significance
Conservation
PhyloP100: 0.243
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESRRB | NM_001379180.1 | c.689-10G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000644823.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESRRB | ENST00000644823.1 | c.689-10G>A | splice_polypyrimidine_tract_variant, intron_variant | NM_001379180.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152060Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251326Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135836
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GnomAD4 exome AF: 0.0000882 AC: 129AN: 1461876Hom.: 0 Cov.: 32 AF XY: 0.0000811 AC XY: 59AN XY: 727238
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74380
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
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 | Mar 06, 2014 | Variant classified as Uncertain Significance - Favor Benign. The 626-10G>A varia nt in ESRRB has not been previously reported in individuals with hearing loss an d was absent from large population studies. This variant is located in the 3' sp lice region, but is not located in the invariant (-1/-2) positions in the splice site consensus sequence. Computational tools do not suggest an impact to splici ng; however, this information is not predictive enough to rule out pathogenicity . In summary, the clinical significance of this variant cannot be determine with certainty; however based upon the computational data, we lean towards a more li kely benign role. - |
Autosomal recessive nonsyndromic hearing loss 35 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at