rs200237229
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The ENST00000509242.5(ESRRB):c.1427G>A(p.Arg476His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00078 in 1,582,166 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R476C) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000509242.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESRRB | NM_001379180.1 | c.*1535G>A | 3_prime_UTR_variant | 7/7 | ENST00000644823.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESRRB | ENST00000644823.1 | c.*1535G>A | 3_prime_UTR_variant | 7/7 | NM_001379180.1 | P1 | |||
ENST00000554926.1 | n.414+2164C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000552 AC: 84AN: 152080Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000457 AC: 90AN: 196962Hom.: 1 AF XY: 0.000345 AC XY: 36AN XY: 104430
GnomAD4 exome AF: 0.000804 AC: 1150AN: 1430086Hom.: 3 Cov.: 31 AF XY: 0.000753 AC XY: 533AN XY: 707938
GnomAD4 genome ? AF: 0.000552 AC: 84AN: 152080Hom.: 0 Cov.: 33 AF XY: 0.000485 AC XY: 36AN XY: 74270
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 13, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 02, 2018 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 24, 2017 | p.Arg476His in exon 10 of ESRRB: This variant is not expected to have clinical s ignificance because the arginine (Arg) at position 476 is not conserved across m ammals and the change to histidine (His) is present in several species including chimp. In addition, this variant has been identified in 0.1% (81/96870) of Euro pean chromosomes including 1 homozygote by the Genome Aggregation Database (gnom AD, http://gnomad.broadinstitute.org/; dbSNP rs200237229). - |
Likely benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Aug 24, 2015 | - - |
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at