rs9310736

Variant names:

• chr3-24309320-A-G
• rs9310736
• NM_001354712.2:c.-188-11949T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-24309320-A-G
• chr3-24309320-A-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.-188-11949T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,160 control chromosomes in the GnomAD database, including 36,761 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 0.69 (36761 hom., cov: 33)
• Consequence: THRB NM_001354712.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 29 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: AD Classification: STRONG Submitted by: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THRB	NM_001354712.2	c.-188-11949T>C		intron_variant	Intron 2 of 10	ENST00000646209.2	NP_001341641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THRB	ENST00000646209.2	c.-188-11949T>C		intron_variant	Intron 2 of 10		NM_001354712.2	ENSP00000496686.2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105258 AN: 152042 Hom.: 36709 Cov.: 33

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.692 AC: 105366 AN: 152160 Hom.: 36761 Cov.: 33 AF XY: 0.695 AC XY: 51721 AN XY: 74400

African (AFR) AF: 0.739 AC: 30674 AN: 41506

American (AMR) AF: 0.737 AC: 11259 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2078 AN: 3470

East Asian (EAS) AF: 0.792 AC: 4106 AN: 5184

South Asian (SAS) AF: 0.664 AC: 3201 AN: 4818

European-Finnish (FIN) AF: 0.650 AC: 6884 AN: 10586

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.660 AC: 44902 AN: 67998

Other (OTH) AF: 0.661 AC: 1395 AN: 2112

Alfa AF: 0.671 Hom.: 162470

Bravo AF: 0.700

Asia WGS AF: 0.722 AC: 2513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.6
DANN	Benign	0.57
PhyloP100		1.6
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: rs9310736; hg19: chr3-24350811;