rs939348

Positions:

• chr17-40075600-T-C
• chr17-40075600-T-G

Variant summary

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

The NM_199334.5(THRA):​c.53+1059T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,158 control chromosomes in the GnomAD database, including 37,420 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 0.70 (37420 hom., cov: 33)
• Consequence: THRA NM_199334.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THRA	NM_199334.5	c.53+1059T>C		intron_variant		ENST00000450525.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THRA	ENST00000450525.7	c.53+1059T>C		intron_variant		1	NM_199334.5	P1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106199 AN: 152040 Hom.: 37403 Cov.: 33

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.710

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.698 AC: 106260 AN: 152158 Hom.: 37420 Cov.: 33 AF XY: 0.694 AC XY: 51646 AN XY: 74382

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.708

Alfa AF: 0.712 Hom.: 20750

Bravo AF: 0.704

Asia WGS AF: 0.568 AC: 1979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.2
DANN	Benign	0.54

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: rs939348; hg19: chr17-38231853;