rs2596622

chr3-24163401-T-C

Variant summary

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

The NM_001354712.2(THRB):c.284-10911A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,974 control chromosomes in the GnomAD database, including 7,830 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 0.31 (7830 hom., cov: 32)
• Consequence: THRB NM_001354712.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141

Genes affected

THRB (HGNC:11799): (thyroid hormone receptor beta) 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. Mutations in this gene are known to be a cause of generalized thyroid hormone resistance (GTHR), a syndrome characterized by goiter and high levels of circulating thyroid hormone (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH). Several alternatively spliced transcript variants encoding the same protein have been observed for this gene. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THRB	NM_001354712.2	c.284-10911A>G		intron_variant		ENST00000646209.2
THRB-AS2	NR_121667.1	n.78-10383T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THRB	ENST00000646209.2	c.284-10911A>G		intron_variant			NM_001354712.2
	ENST00000702841.1	n.84-10383T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47069 AN: 151856 Hom.: 7802 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.310 AC: 47159 AN: 151974 Hom.: 7830 Cov.: 32 AF XY: 0.309 AC XY: 22943 AN XY: 74308

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.310

Alfa AF: 0.306 Hom.: 1182

Bravo AF: 0.330

Asia WGS AF: 0.364 AC: 1263 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	13
Dann	Benign	0.83

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: rs2596622; hg19: chr3-24204892;