chr8-132948746-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003235.5(TG):c.5234-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,611,312 control chromosomes in the GnomAD database, including 503,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.80 ( 48190 hom., cov: 31)
Exomes 𝑓: 0.79 ( 455333 hom. )
Consequence
TG
NM_003235.5 intron
NM_003235.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.60
Genes affected
TG (HGNC:11764): (thyroglobulin) Thyroglobulin (Tg) is a glycoprotein homodimer produced predominantly by the thryroid gland. It acts as a substrate for the synthesis of thyroxine and triiodothyronine as well as the storage of the inactive forms of thyroid hormone and iodine. Thyroglobulin is secreted from the endoplasmic reticulum to its site of iodination, and subsequent thyroxine biosynthesis, in the follicular lumen. Mutations in this gene cause thyroid dyshormonogenesis, manifested as goiter, and are associated with moderate to severe congenital hypothyroidism. Polymorphisms in this gene are associated with susceptibility to autoimmune thyroid diseases (AITD) such as Graves disease and Hashimoto thryoiditis. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant 8-132948746-C-T is Benign according to our data. Variant chr8-132948746-C-T is described in ClinVar as [Benign]. Clinvar id is 1246261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TG | NM_003235.5 | c.5234-30C>T | intron_variant | ENST00000220616.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TG | ENST00000220616.9 | c.5234-30C>T | intron_variant | 1 | NM_003235.5 | P1 | |||
TG | ENST00000523756.5 | c.*1447-30C>T | intron_variant, NMD_transcript_variant | 1 | |||||
TG | ENST00000519178.5 | c.600-30C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.796 AC: 120903AN: 151968Hom.: 48152 Cov.: 31
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GnomAD3 exomes AF: 0.808 AC: 203189AN: 251320Hom.: 82372 AF XY: 0.807 AC XY: 109660AN XY: 135852
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GnomAD4 exome AF: 0.789 AC: 1151730AN: 1459226Hom.: 455333 Cov.: 38 AF XY: 0.790 AC XY: 573633AN XY: 726010
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GnomAD4 genome AF: 0.796 AC: 120988AN: 152086Hom.: 48190 Cov.: 31 AF XY: 0.797 AC XY: 59228AN XY: 74322
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Iodotyrosyl coupling defect Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at