rs62065216

Positions:

• chr17-40062520-G-A
• chr17-40062520-G-C

Variant summary

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

The ENST00000578218.5(THRA):​c.-326G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,884 control chromosomes in the GnomAD database, including 11,305 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 0.38 (11303 hom., cov: 30)
  • Exomes 𝑓: 0.39 (2 hom.)
• Consequence: THRA ENST00000578218.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THRA	NM_001190919.2	c.-298+69G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THRA	ENST00000578218.5	c.-326G>A		5_prime_UTR_variant	1/5	4
THRA	ENST00000394121.8	c.-298+69G>A		intron_variant		2
THRA	ENST00000577288.5	c.-298+4042G>A		intron_variant		4
THRA	ENST00000585047.5	c.-298+558G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57130 AN: 151738 Hom.: 11284 Cov.: 30

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.365

GnomAD4 exome AF: 0.393 AC: 11 AN: 28 Hom.: 2 Cov.: 0 AF XY: 0.450 AC XY: 9 AN XY: 20

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.438

GnomAD4 genome AF: 0.377 AC: 57181 AN: 151856 Hom.: 11303 Cov.: 30 AF XY: 0.377 AC XY: 27956 AN XY: 74178

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.368

Alfa AF: 0.399 Hom.: 2754

Bravo AF: 0.363

Asia WGS AF: 0.398 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	16
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62065216; hg19: chr17-38218773;