14-81108501-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000554263.5(TSHR):c.*45T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.02 in 1,505,526 control chromosomes in the GnomAD database, including 521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 26 hom., cov: 25)
Exomes 𝑓: 0.021 ( 495 hom. )
Consequence
TSHR
ENST00000554263.5 3_prime_UTR
ENST00000554263.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0880
Genes affected
TSHR (HGNC:12373): (thyroid stimulating hormone receptor) The protein encoded by this gene is a membrane protein and a major controller of thyroid cell metabolism. The encoded protein is a receptor for thyrothropin and thyrostimulin, and its activity is mediated by adenylate cyclase. Defects in this gene are a cause of several types of hyperthyroidism. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
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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=-0.86).
BP6
?
Variant 14-81108501-T-C is Benign according to our data. Variant chr14-81108501-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 403571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0143 (2088/146066) while in subpopulation NFE AF= 0.0214 (1427/66558). AF 95% confidence interval is 0.0205. There are 26 homozygotes in gnomad4. There are 966 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 26 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSHR | NM_000369.5 | c.692+49T>C | intron_variant | ENST00000298171.7 | |||
LOC101928462 | XR_001751022.2 | n.488-8975A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSHR | ENST00000298171.7 | c.692+49T>C | intron_variant | 1 | NM_000369.5 | P1 | |||
ENST00000646052.2 | n.511-8975A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0143 AC: 2088AN: 146018Hom.: 26 Cov.: 25
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GnomAD4 exome AF: 0.0206 AC: 28014AN: 1359460Hom.: 495 Cov.: 34 AF XY: 0.0202 AC XY: 13676AN XY: 676716
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: classification based on high MAF (>1% in 1000Genomes), outside of splice consensus sequence and lack of conservation - |
Familial gestational hyperthyroidism Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Hypothyroidism due to TSH receptor mutations Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Familial hyperthyroidism due to mutations in TSH receptor Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
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