14-76371349-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004452.4(ESRRB):c.-369G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000886 in 152,412 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 0.00088 ( 0 hom., cov: 32)
Exomes 𝑓: 0.010 ( 0 hom. )
Consequence
ESRRB
NM_004452.4 5_prime_UTR
NM_004452.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.927
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=-0.9).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ESRRB | NM_004452.4 | c.-369G>A | 5_prime_UTR_variant | 1/11 | NP_004443.3 | |||
ESRRB | NM_001411038.1 | c.2+60433G>A | intron_variant | NP_001397967.1 | ||||
ESRRB | XM_047431079.1 | c.-67-36194G>A | intron_variant | XP_047287035.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ESRRB | ENST00000380887.7 | c.-369G>A | 5_prime_UTR_variant | 1/11 | 5 | ENSP00000370270 | ||||
ESRRB | ENST00000512784.6 | c.2+60433G>A | intron_variant | 5 | ENSP00000424992 | |||||
ESRRB | ENST00000505752.6 | upstream_gene_variant | 1 | ENSP00000423004 |
Frequencies
GnomAD3 genomes AF: 0.000887 AC: 135AN: 152194Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0100 AC: 1AN: 100Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 74
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GnomAD4 genome AF: 0.000880 AC: 134AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.000993 AC XY: 74AN XY: 74492
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 35 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at