rs12939700

Positions:

• chr17-40089538-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_199334.5(THRA):​c.*82C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 1,524,054 control chromosomes in the GnomAD database, including 2,715 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.073 (643 hom., cov: 31)
  • Exomes 𝑓: 0.050 (2072 hom.)
• Consequence: THRA NM_199334.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

Genes affected

THRA (HGNC:11796): (thyroid hormone receptor alpha) 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. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THRA	NM_199334.5	c.*82C>A		3_prime_UTR_variant	9/9	ENST00000450525.7	NP_955366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THRA	ENST00000450525.7	c.*82C>A		3_prime_UTR_variant	9/9	1	NM_199334.5	ENSP00000395641	P1

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11057 AN: 152000 Hom.: 635 Cov.: 31

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0358

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.00425

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.0651

GnomAD4 exome AF: 0.0496 AC: 68022 AN: 1371936 Hom.: 2072 Cov.: 31 AF XY: 0.0484 AC XY: 32657 AN XY: 674662

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.0258

Gnomad4 ASJ exome AF: 0.0296

Gnomad4 EAS exome AF: 0.00280

Gnomad4 SAS exome AF: 0.0380

Gnomad4 FIN exome AF: 0.0473

Gnomad4 NFE exome AF: 0.0503

Gnomad4 OTH exome AF: 0.0502

GnomAD4 genome AF: 0.0730 AC: 11104 AN: 152118 Hom.: 643 Cov.: 31 AF XY: 0.0700 AC XY: 5206 AN XY: 74374

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0357

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.00426

Gnomad4 SAS AF: 0.0313

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0491

Gnomad4 OTH AF: 0.0644

Alfa AF: 0.0523 Hom.: 192

Bravo AF: 0.0754

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12939700; hg19: chr17-38245791;