3-24143699-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7
The NM_001354712.2(THRB):c.540G>A(p.Leu180Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,614,016 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000095 ( 0 hom. )
Consequence
THRB
NM_001354712.2 synonymous
NM_001354712.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.40
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 Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 3-24143699-C-T is Benign according to our data. Variant chr3-24143699-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3768578.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=3.4 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
THRB | NM_001354712.2 | c.540G>A | p.Leu180Leu | synonymous_variant | Exon 8 of 11 | ENST00000646209.2 | NP_001341641.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000559 AC: 14AN: 250574Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135388
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GnomAD4 exome AF: 0.0000951 AC: 139AN: 1461854Hom.: 0 Cov.: 32 AF XY: 0.0000839 AC XY: 61AN XY: 727232
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74316
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Feb 12, 2025
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Benign
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at