rs3752874
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001354712.2(THRB):c.735C>T(p.Phe245=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,613,814 control chromosomes in the GnomAD database, including 20,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.15 ( 1852 hom., cov: 32)
Exomes 𝑓: 0.15 ( 18266 hom. )
Consequence
THRB
NM_001354712.2 synonymous
NM_001354712.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.64
Genes affected
THRB (HGNC:11799): (thyroid hormone receptor beta) The protein encoded by this gene is a nuclear hormone receptor for triiodothyronine. It is one of the several receptors for thyroid hormone, and has been shown to mediate the biological activities of thyroid hormone. Knockout studies in mice suggest that the different receptors, while having certain extent of redundancy, may mediate different functions of thyroid hormone. Mutations in this gene are known to be a cause of generalized thyroid hormone resistance (GTHR), a syndrome characterized by goiter and high levels of circulating thyroid hormone (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH). Several alternatively spliced transcript variants encoding the same protein have been observed for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 3-24143504-G-A is Benign according to our data. Variant chr3-24143504-G-A is described in ClinVar as [Benign]. Clinvar id is 198422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-24143504-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.64 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THRB | NM_001354712.2 | c.735C>T | p.Phe245= | synonymous_variant | 8/11 | ENST00000646209.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THRB | ENST00000646209.2 | c.735C>T | p.Phe245= | synonymous_variant | 8/11 | NM_001354712.2 | |||
ENST00000702841.1 | n.83+5556G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.151 AC: 22919AN: 152096Hom.: 1854 Cov.: 32
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GnomAD3 exomes AF: 0.155 AC: 38775AN: 250376Hom.: 3277 AF XY: 0.158 AC XY: 21456AN XY: 135410
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GnomAD4 exome AF: 0.155 AC: 226225AN: 1461600Hom.: 18266 Cov.: 32 AF XY: 0.157 AC XY: 114142AN XY: 727112
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GnomAD4 genome ? AF: 0.151 AC: 22912AN: 152214Hom.: 1852 Cov.: 32 AF XY: 0.150 AC XY: 11143AN XY: 74416
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 17, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Thyroid hormone resistance, generalized, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at