chr3-24491787-G-A

Position:

• chr3-24491787-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001354712.2(THRB):​c.-261+2865C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,062 control chromosomes in the GnomAD database, including 16,676 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 0.46 (16676 hom., cov: 33)
• Consequence: THRB NM_001354712.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THRB	NM_001354712.2	c.-261+2865C>T		intron_variant		ENST00000646209.2	NP_001341641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THRB	ENST00000646209.2	c.-261+2865C>T		intron_variant			NM_001354712.2	ENSP00000496686.2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70349 AN: 151944 Hom.: 16678 Cov.: 33

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.463 AC: 70360 AN: 152062 Hom.: 16676 Cov.: 33 AF XY: 0.460 AC XY: 34197 AN XY: 74334

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.464

Alfa AF: 0.504 Hom.: 19438

Bravo AF: 0.456

Asia WGS AF: 0.378 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.62

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: rs2196427; hg19: chr3-24533278;