chr3-24184379-G-A

Variant names:

• chr3-24184379-G-A
• rs826216
• NM_001354712.2:c.283+5695C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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-AS2 (HGNC:):

THRB-AS2 (HGNC:54854): (THRB antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THRB	NM_001354712.2	MANE Select	c.283+5695C>T		intron	N/A	NP_001341641.1
	THRB	NM_000461.5		c.283+5695C>T		intron	N/A	NP_000452.2
	THRB	NM_001128176.3		c.283+5695C>T		intron	N/A	NP_001121648.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THRB	ENST00000646209.2	MANE Select	c.283+5695C>T		intron	N/A	ENSP00000496686.2
	THRB	ENST00000356447.9	TSL:1	c.283+5695C>T		intron	N/A	ENSP00000348827.4
	THRB	ENST00000447875.5	TSL:1	c.283+5695C>T		intron	N/A	ENSP00000388467.1

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

African (AFR) AF: 0.637 AC: 26381 AN: 41436

American (AMR) AF: 0.429 AC: 6559 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3470

East Asian (EAS) AF: 0.375 AC: 1936 AN: 5168

South Asian (SAS) AF: 0.467 AC: 2249 AN: 4816

European-Finnish (FIN) AF: 0.275 AC: 2911 AN: 10574

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22166 AN: 67962

Other (OTH) AF: 0.406 AC: 857 AN: 2112

Alfa AF: 0.354 Hom.: 43817

Bravo AF: 0.442

Asia WGS AF: 0.520 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.52
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs826216; hg19: chr3-24225870;