3-24146667-C-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_001354712.2(THRB):c.532+8G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,613,980 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001354712.2 splice_region, intron
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
THRB | NM_001354712.2 | c.532+8G>C | splice_region_variant, intron_variant | Intron 7 of 10 | ENST00000646209.2 | NP_001341641.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00105 AC: 160AN: 152232Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000279 AC: 70AN: 251144Hom.: 0 AF XY: 0.000169 AC XY: 23AN XY: 135724
GnomAD4 exome AF: 0.000105 AC: 154AN: 1461630Hom.: 0 Cov.: 31 AF XY: 0.0000798 AC XY: 58AN XY: 727120
GnomAD4 genome AF: 0.00106 AC: 161AN: 152350Hom.: 1 Cov.: 32 AF XY: 0.00105 AC XY: 78AN XY: 74498
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
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not specified Benign:1
Variant summary: THRB c.532+8G>C alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00028 in 251144 control chromosomes, predominantly at a frequency of 0.004 within the African or African-American subpopulation in the gnomAD database, suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.532+8G>C in individuals affected with Thyroid Hormone Resistance, Generalized, Autosomal Dominant and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 592487). Based on the evidence outlined above, the variant was classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at