rs1568400

chr17-40064855-T-C

Variant summary

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

The NM_199334.5(THRA):c.-298+1763T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,000 control chromosomes in the GnomAD database, including 13,543 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 (13543 hom., cov: 31)
• Consequence: THRA NM_199334.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THRA	NM_199334.5	c.-298+1763T>C		intron_variant		ENST00000450525.7
THRA	NM_001190918.2	c.-298+1763T>C		intron_variant
THRA	NM_001190919.2	c.-298+2404T>C		intron_variant
THRA	NM_003250.6	c.-298+1763T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THRA	ENST00000450525.7	c.-298+1763T>C		intron_variant		1	NM_199334.5	P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57341 AN: 151882 Hom.: 13521 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.378 AC: 57412 AN: 152000 Hom.: 13543 Cov.: 31 AF XY: 0.379 AC XY: 28118 AN XY: 74274

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.344

Alfa AF: 0.260 Hom.: 6903

Bravo AF: 0.409

Asia WGS AF: 0.271 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.5
Dann	Benign	0.42

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: rs1568400; hg19: chr17-38221108;