rs9809150

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001354712.2(THRB):​c.-260-40697A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,008 control chromosomes in the GnomAD database, including 39,765 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 0.72 ( 39765 hom., cov: 31)

Consequence

THRB
NM_001354712.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00700
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THRBNM_001354712.2 linkuse as main transcriptc.-260-40697A>G intron_variant ENST00000646209.2 NP_001341641.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
THRBENST00000646209.2 linkuse as main transcriptc.-260-40697A>G intron_variant NM_001354712.2 ENSP00000496686 P10828-1

Frequencies

GnomAD3 genomes
AF:
0.718
AC:
109109
AN:
151890
Hom.:
39726
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.834
Gnomad AMI
AF:
0.651
Gnomad AMR
AF:
0.693
Gnomad ASJ
AF:
0.612
Gnomad EAS
AF:
0.576
Gnomad SAS
AF:
0.697
Gnomad FIN
AF:
0.695
Gnomad MID
AF:
0.598
Gnomad NFE
AF:
0.677
Gnomad OTH
AF:
0.693
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.718
AC:
109206
AN:
152008
Hom.:
39765
Cov.:
31
AF XY:
0.717
AC XY:
53259
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.834
Gnomad4 AMR
AF:
0.693
Gnomad4 ASJ
AF:
0.612
Gnomad4 EAS
AF:
0.577
Gnomad4 SAS
AF:
0.696
Gnomad4 FIN
AF:
0.695
Gnomad4 NFE
AF:
0.677
Gnomad4 OTH
AF:
0.693
Alfa
AF:
0.681
Hom.:
48468
Bravo
AF:
0.720
Asia WGS
AF:
0.603
AC:
2102
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
6.3
DANN
Benign
0.78

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9809150; hg19: chr3-24419559; API