3-24143816-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000289130 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THRB	NM_001354712.2	c.533-110G>A		intron_variant	Intron 7 of 10	ENST00000646209.2	NP_001341641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THRB	ENST00000646209.2	c.533-110G>A		intron_variant	Intron 7 of 10		NM_001354712.2	ENSP00000496686.2

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

Gnomad4 AFR exome AF: 0.423

Gnomad4 AMR exome AF: 0.249

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.0946

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.287

Gnomad4 OTH exome AF: 0.295

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

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.314

Alfa AF: 0.305 Hom.: 889

Bravo AF: 0.328

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs3772382; hg19: chr3-24185307;