rs3744805

chr17-40092101-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199334.5(THRA):c.*2645C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,012 control chromosomes in the GnomAD database, including 3,618 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 0.20 (3614 hom., cov: 30)
  • Exomes 𝑓: 0.088 (4 hom.)
• Consequence: THRA NM_199334.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THRA	NM_199334.5	c.*2645C>T		3_prime_UTR_variant	9/9	ENST00000450525.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THRA	ENST00000450525.7	c.*2645C>T		3_prime_UTR_variant	9/9	1	NM_199334.5	P1
THRA	ENST00000264637.8	c.1111-919C>T		intron_variant		1
THRA	ENST00000584985.5	c.1111-1036C>T		intron_variant		1
THRA	ENST00000394121.8	c.1111-919C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29575 AN: 151620 Hom.: 3608 Cov.: 30

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.0880 AC: 25 AN: 284 Hom.: 4 Cov.: 0 AF XY: 0.0901 AC XY: 20 AN XY: 222

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0588

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.195 AC: 29615 AN: 151728 Hom.: 3614 Cov.: 30 AF XY: 0.200 AC XY: 14857 AN XY: 74160

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.175

Alfa AF: 0.134 Hom.: 1683

Bravo AF: 0.201

Asia WGS AF: 0.323 AC: 1119 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	18
Dann	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3744805; hg19: chr17-38248354;