chr3-24143816-C-T

Variant names:

• chr3-24143816-C-T
• rs3772382
• NM_001354712.2:c.533-110G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001354712.2(THRB):​c.533-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,134,462 control chromosomes in the GnomAD database, including 50,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8315 hom., cov: 32)
  • Exomes 𝑓: 0.29 (42488 hom.)
• Consequence: THRB NM_001354712.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.118
• Publications: 3 publications found

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]

THRB Gene-Disease associations (from GenCC):

• thyroid hormone resistance, generalized, autosomal dominant

  Inheritance: SD, AD Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• thyroid hormone resistance, generalized, autosomal recessive

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

THRB-AS2 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-24143816-C-T is Benign according to our data. Variant chr3-24143816-C-T is described in ClinVar as Benign. ClinVar VariationId is 1228292.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354712.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THRB	NM_001354712.2	MANE Select	c.533-110G>A		intron	N/A	NP_001341641.1	P10828-1
	THRB	NM_000461.5		c.533-110G>A		intron	N/A	NP_000452.2
	THRB	NM_001128176.3		c.533-110G>A		intron	N/A	NP_001121648.1	P10828-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THRB	ENST00000646209.2	MANE Select	c.533-110G>A		intron	N/A	ENSP00000496686.2	P10828-1
	THRB	ENST00000356447.9	TSL:1	c.533-110G>A		intron	N/A	ENSP00000348827.4	P10828-1
	THRB	ENST00000280696.9	TSL:5	c.578-110G>A		intron	N/A	ENSP00000280696.5	P10828-2

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48751 AN: 151828 Hom.: 8302 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.318

GnomAD4 exome AF: 0.287 AC: 282048 AN: 982516 Hom.: 42488 Cov.: 13 AF XY: 0.289 AC XY: 146136 AN XY: 504838

African (AFR) AF: 0.423 AC: 10300 AN: 24344

American (AMR) AF: 0.249 AC: 9635 AN: 38694

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 7664 AN: 22760

East Asian (EAS) AF: 0.0946 AC: 3456 AN: 36546

South Asian (SAS) AF: 0.346 AC: 25496 AN: 73780

European-Finnish (FIN) AF: 0.279 AC: 11297 AN: 40534

Middle Eastern (MID) AF: 0.290 AC: 1287 AN: 4444

European-Non Finnish (NFE) AF: 0.287 AC: 199688 AN: 696598

Other (OTH) AF: 0.295 AC: 13225 AN: 44816

GnomAD4 genome AF: 0.321 AC: 48788 AN: 151946 Hom.: 8315 Cov.: 32 AF XY: 0.317 AC XY: 23574 AN XY: 74280

African (AFR) AF: 0.425 AC: 17586 AN: 41398

American (AMR) AF: 0.294 AC: 4496 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3470

East Asian (EAS) AF: 0.111 AC: 572 AN: 5154

South Asian (SAS) AF: 0.334 AC: 1602 AN: 4802

European-Finnish (FIN) AF: 0.251 AC: 2662 AN: 10586

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19780 AN: 67932

Other (OTH) AF: 0.314 AC: 661 AN: 2104

Alfa AF: 0.305 Hom.: 889

Bravo AF: 0.328

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.59
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3772382; hg19: chr3-24185307;