NM_001354712.2:c.283+4390C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001354712.2(THRB):​c.283+4390C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,898 control chromosomes in the GnomAD database, including 11,153 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 0.37 ( 11153 hom., cov: 31)

Consequence

THRB
NM_001354712.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.190

Publications

3 publications found
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]
THRB-AS2 (HGNC:54854): (THRB antisense RNA 2)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
THRBNM_001354712.2 linkc.283+4390C>T intron_variant Intron 5 of 10 ENST00000646209.2 NP_001341641.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
THRBENST00000646209.2 linkc.283+4390C>T intron_variant Intron 5 of 10 NM_001354712.2 ENSP00000496686.2 P10828-1

Frequencies

GnomAD3 genomes
AF:
0.374
AC:
56786
AN:
151780
Hom.:
11148
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.497
Gnomad AMI
AF:
0.240
Gnomad AMR
AF:
0.336
Gnomad ASJ
AF:
0.316
Gnomad EAS
AF:
0.208
Gnomad SAS
AF:
0.379
Gnomad FIN
AF:
0.333
Gnomad MID
AF:
0.339
Gnomad NFE
AF:
0.332
Gnomad OTH
AF:
0.368
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.374
AC:
56820
AN:
151898
Hom.:
11153
Cov.:
31
AF XY:
0.374
AC XY:
27766
AN XY:
74244
show subpopulations
African (AFR)
AF:
0.497
AC:
20572
AN:
41384
American (AMR)
AF:
0.336
AC:
5120
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
0.316
AC:
1095
AN:
3466
East Asian (EAS)
AF:
0.209
AC:
1077
AN:
5160
South Asian (SAS)
AF:
0.379
AC:
1826
AN:
4812
European-Finnish (FIN)
AF:
0.333
AC:
3511
AN:
10552
Middle Eastern (MID)
AF:
0.327
AC:
96
AN:
294
European-Non Finnish (NFE)
AF:
0.332
AC:
22537
AN:
67952
Other (OTH)
AF:
0.364
AC:
768
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1777
3554
5330
7107
8884
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
542
1084
1626
2168
2710
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.345
Hom.:
15113
Bravo
AF:
0.380
Asia WGS
AF:
0.286
AC:
998
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
2.3
DANN
Benign
0.68
PhyloP100
0.19
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

Publications

Other links and lift over

dbSNP: rs12639293; hg19: chr3-24227175; API