3-24163167-G-C

Variant names:

• chr3-24163167-G-C
• rs77624520
• NM_001354712.2:c.284-10677C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001354712.2(THRB):​c.284-10677C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 152,246 control chromosomes in the GnomAD database, including 167 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 0.032 (167 hom., cov: 32)
• Consequence: THRB NM_001354712.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0791 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.284-10677C>G		intron	N/A	NP_001341641.1	P10828-1
	THRB	NM_000461.5		c.284-10677C>G		intron	N/A	NP_000452.2
	THRB	NM_001128176.3		c.284-10677C>G		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.284-10677C>G		intron	N/A	ENSP00000496686.2	P10828-1
	THRB	ENST00000356447.9	TSL:1	c.284-10677C>G		intron	N/A	ENSP00000348827.4	P10828-1
	THRB	ENST00000447875.5	TSL:1	c.284-10677C>G		intron	N/A	ENSP00000388467.1	A0A0C4DG57

Frequencies

GnomAD3 genomes AF: 0.0315 AC: 4793 AN: 152128 Hom.: 166 Cov.: 32

Gnomad AFR AF: 0.0814

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0178

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.0314

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00811

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0311

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

GnomAD4 genome AF: 0.0316 AC: 4805 AN: 152246 Hom.: 167 Cov.: 32 AF XY: 0.0311 AC XY: 2318 AN XY: 74440

African (AFR) AF: 0.0814 AC: 3382 AN: 41544

American (AMR) AF: 0.0178 AC: 272 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3464

East Asian (EAS) AF: 0.0317 AC: 164 AN: 5180

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4824

European-Finnish (FIN) AF: 0.00811 AC: 86 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0106 AC: 722 AN: 68020

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.00745 Hom.: 1

Bravo AF: 0.0345

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Benign	0.68
PhyloP100		3.0
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: rs77624520; hg19: chr3-24204658;