rs28912996
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001206744.2(TPO):c.2387-17C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,614,126 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0035 ( 10 hom., cov: 33)
Exomes 𝑓: 0.0024 ( 77 hom. )
Consequence
TPO
NM_001206744.2 splice_polypyrimidine_tract, intron
NM_001206744.2 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.535
Genes affected
TPO (HGNC:12015): (thyroid peroxidase) This gene encodes a membrane-bound glycoprotein. The encoded protein acts as an enzyme and plays a central role in thyroid gland function. The protein functions in the iodination of tyrosine residues in thyroglobulin and phenoxy-ester formation between pairs of iodinated tyrosines to generate the thyroid hormones, thyroxine and triiodothyronine. Mutations in this gene are associated with several disorders of thyroid hormonogenesis, including congenital hypothyroidism, congenital goiter, and thyroid hormone organification defect IIA. Multiple transcript variants encoding distinct isoforms have been identified for this gene, but the full-length nature of some variants has not been determined. [provided by RefSeq, May 2011]
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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=-0.9).
BP6
?
Variant 2-1503931-C-T is Benign according to our data. Variant chr2-1503931-C-T is described in ClinVar as [Benign]. Clinvar id is 256613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-1503931-C-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00353 (538/152296) while in subpopulation EAS AF= 0.0414 (214/5164). AF 95% confidence interval is 0.0369. There are 10 homozygotes in gnomad4. There are 305 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPO | NM_001206744.2 | c.2387-17C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000329066.9 | |||
LOC124905966 | XR_007086185.1 | n.167-17740G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPO | ENST00000329066.9 | c.2387-17C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001206744.2 | P1 | |||
ENST00000650512.1 | n.547+76270G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00353 AC: 537AN: 152178Hom.: 10 Cov.: 33
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GnomAD3 exomes AF: 0.00774 AC: 1943AN: 251192Hom.: 43 AF XY: 0.00667 AC XY: 906AN XY: 135810
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GnomAD4 exome AF: 0.00239 AC: 3488AN: 1461830Hom.: 77 Cov.: 31 AF XY: 0.00230 AC XY: 1670AN XY: 727212
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GnomAD4 genome ? AF: 0.00353 AC: 538AN: 152296Hom.: 10 Cov.: 33 AF XY: 0.00410 AC XY: 305AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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