3-24163519-G-A

Variant names:

• chr3-24163519-G-A
• rs6798561
• NM_001354712.2:c.284-11029C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000461.5(THRB):​c.284-11029C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 152,200 control chromosomes in the GnomAD database, including 63 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 0.016 (63 hom., cov: 33)
• Consequence: THRB NM_000461.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.815
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000461.5. 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.284-11029C>T		intron	N/A	NP_001341641.1
	THRB	NM_000461.5		c.284-11029C>T		intron	N/A	NP_000452.2
	THRB	NM_001128176.3		c.284-11029C>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.284-11029C>T		intron	N/A	ENSP00000496686.2
	THRB	ENST00000356447.9	TSL:1	c.284-11029C>T		intron	N/A	ENSP00000348827.4
	THRB	ENST00000447875.5	TSL:1	c.284-11029C>T		intron	N/A	ENSP00000388467.1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2397 AN: 152084 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00918

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0167

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

GnomAD4 genome AF: 0.0158 AC: 2411 AN: 152200 Hom.: 63 Cov.: 33 AF XY: 0.0149 AC XY: 1112 AN XY: 74406

African (AFR) AF: 0.0536 AC: 2225 AN: 41534

American (AMR) AF: 0.00910 AC: 139 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67992

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0176 Hom.: 5

Bravo AF: 0.0191

Asia WGS AF: 0.00347 AC: 12 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.37
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism

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: rs6798561; hg19: chr3-24205010;