rs826216

Positions:

• chr3-24184379-G-A

Variant summary

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

The NM_001354712.2(THRB):​c.283+5695C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,024 control chromosomes in the GnomAD database, including 15,241 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 0.42 (15241 hom., cov: 32)
• Consequence: THRB NM_001354712.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.984

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THRB	NM_001354712.2	c.283+5695C>T		intron_variant		ENST00000646209.2	NP_001341641.1
THRB-AS2	NR_121667.1	n.262-5196G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THRB	ENST00000646209.2	c.283+5695C>T		intron_variant			NM_001354712.2	ENSP00000496686
	ENST00000702841.1	n.267+6367G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64354 AN: 151906 Hom.: 15188 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.424 AC: 64483 AN: 152024 Hom.: 15241 Cov.: 32 AF XY: 0.423 AC XY: 31436 AN XY: 74308

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.406

Alfa AF: 0.340 Hom.: 19431

Bravo AF: 0.442

Asia WGS AF: 0.520 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.52

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: rs826216; hg19: chr3-24225870;